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image of Biological Targets in Leishmaniasis and the Identification of the Next

Abstract

With increasing mortality and morbidity, leishmaniasis remains a global health burden. The lack of vaccines and limited drug options for treatment, each with low efficacy and severe toxicities, highlights the urgent need for new therapeutics. Our review of 260 articles (1981-2025) provides comprehensive insights, emphasizing the critical identification and characterization of viable biological targets in Leishmania for efficient drug development. We summarize the various strategies utilized in the drug design pipeline, detailing how these approaches have revealed key biological targets involved in parasite survival, virulence, and pathogenesis, and have identified promising inhibitors across metabolic and non-metabolic pathways. We report the biochemical reactions and inhibitory activities (IC) of these compounds against their respective targets. Additionally, we outline the synthetic strategies for key chemotypes and identify ongoing challenges and future directions in antileishmanial agent research. Importantly, our review evaluates multitarget inhibitors, highlighting their pros and cons and proposing actionable steps to leverage these molecules to overcome leishmaniasis.

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2026-01-08
2026-02-02

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References

  1. Vankalakunti M. Jha P.K. Siddini V. Babu K. Ballal S.H. Postrenal transplant laryngeal and visceral leishmaniasis - A case report and review of the literature. Indian J. Nephrol. 2012 22 4 301 303 10.4103/0971‑4065.101259 23162277
    [Google Scholar]
  2. Leishmaniasis 2023 Available from: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis
  3. Steverding D. The history of leishmaniasis. Parasit. Vectors 2017 10 1 82 10.1186/s13071‑017‑2028‑5 28202044
    [Google Scholar]
  4. Control of the leishmaniases. World Health Organ. Tech. Rep. Ser. 2010 949 xii xiii 21485694
    [Google Scholar]
  5. Ghorbani M. Farhoudi R. Leishmaniasis in humans: Drug or vaccine therapy? Drug Des. Devel. Ther. 2017 12 25 40 10.2147/DDDT.S146521 29317800
    [Google Scholar]
  6. Alvar J Vélez ID Bern C Leishmaniasis worldwide and global estimates of its incidence PLoS One 2012 7 5 e35671-, 1-e35671, 12. 10.1371/journal.pone.0035671 22693548
    [Google Scholar]
  7. Joshi A.B. Banjara M.R. Chuke S. Assessment of the impact of implementation research on the Visceral Leishmaniasis (VL) elimination efforts in Nepal. PLoS Negl. Trop. Dis. 2023 17 11 0011714 10.1371/journal.pntd.0011714 37943733
    [Google Scholar]
  8. Sousa Silva M. Ferreira A.E.N. Tomás A.M. Cordeiro C. Ponces Freire A. Quantitative assessment of the glyoxalase pathway in Leishmania infantum as a therapeutic target by modelling and computer simulation. FEBS J. 2005 272 10 2388 2398 10.1111/j.1742‑4658.2005.04632.x 15885089
    [Google Scholar]
  9. Pomel S. Cojean S. Loiseau P.M. Targeting sterol metabolism for the development of antileishmanials. Trends Parasitol. 2015 31 1 5 7 10.1016/j.pt.2014.11.007 25498194
    [Google Scholar]
  10. Lionta E. Spyrou G. Vassilatis D. Cournia Z. Structure-based virtual screening for drug discovery: Principles, applications and recent advances. Curr. Top. Med. Chem. 2014 14 16 1923 1938 10.2174/1568026614666140929124445 25262799
    [Google Scholar]
  11. Lage O.M. Ramos M.C. Calisto R. Almeida E. Vasconcelos V. Vicente F. Current screening methodologies in drug discovery for selected human diseases. Mar. Drugs 2018 16 8 279 10.3390/md16080279 30110923
    [Google Scholar]
  12. Padmanabhan P.K. Mukherjee A. Singh S. Glyoxalase I from Leishmania donovani: A potential target for anti-parasite drug. Biochem. Biophys. Res. Commun. 2005 337 4 1237 1248 10.1016/j.bbrc.2005.09.179 16236261
    [Google Scholar]
  13. Borba-Santos L.P. Visbal G. Gagini T. Δ24-sterol methyltransferase plays an important role in the growth and development of Sporothrix schenckii and Sporothrix brasiliensis. Front. Microbiol. 2016 7 311 10.3389/fmicb.2016.00311 27014234
    [Google Scholar]
  14. Nare B. Hardy L.W. Beverley S.M. The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major. J. Biol. Chem. 1997 272 21 13883 13891 10.1074/jbc.272.21.13883 9153248
    [Google Scholar]
  15. Merritt C. Silva L.E. Tanner A.L. Stuart K. Pollastri M.P. Kinases as druggable targets in trypanosomatid protozoan parasites. Chem. Rev. 2014 114 22 11280 11304 10.1021/cr500197d 26443079
    [Google Scholar]
  16. Brumlik M.J. Pandeswara S. Ludwig S.M. Murthy K. Curiel T.J. Parasite mitogen-activated protein kinases as drug discovery targets to treat human protozoan pathogens. J. Signal Transduct. 2011 2011 1 16 10.1155/2011/971968 21637385
    [Google Scholar]
  17. Amewu R.K. Sakyi P.O. Osei-safo D. Synthetic and naturally occurring heterocyclic anticancer compounds with multiple biological targets. Molecules 2021 26 23 7134 10.3390/molecules26237134 34885716
    [Google Scholar]
  18. Newman D.J. Cragg G.M. Natural Products as Sources of New Drugs from 1981 to 2014. J. Nat. Prod. 2016 79 3 629 661 10.1021/acs.jnatprod.5b01055 26852623
    [Google Scholar]
  19. Berdigaliyev N. Aljofan M. An overview of drug discovery and development. Future Med. Chem. 2020 12 10 939 947 10.4155/fmc‑2019‑0307 32270704
    [Google Scholar]
  20. Osorio Y. Travi B.L. Renslo A.R. Peniche A.G. Melby P.C. Identification of small molecule lead compounds for visceral leishmaniasis using a novel ex vivo splenic explant model system. PLoS Negl. Trop. Dis. 2011 5 2 e962 10.1371/journal.pntd.0000962 21358812
    [Google Scholar]
  21. Zhang M.Q. Wilkinson B. Drug discovery beyond the ‘rule-of-five’. Curr. Opin. Biotechnol. 2007 18 6 478 488 10.1016/j.copbio.2007.10.005 18035532
    [Google Scholar]
  22. de la Torre B.G. Albericio F. The pharmaceutical industry in 2021. An analysis of FDA drug approvals from the perspective of molecules. Molecules 2022 27 3 1075 10.3390/molecules27031075 35164339
    [Google Scholar]
  23. Beck H. Härter M. Haß B. Schmeck C. Baerfacker L. Small molecules and their impact in drug discovery: A perspective on the occasion of the 125th anniversary of the Bayer Chemical Research Laboratory. Drug Discov. Today 2022 27 6 1560 1574 10.1016/j.drudis.2022.02.015 35202802
    [Google Scholar]
  24. Dixit K.K. Verma S. Singh O.P. Validation of SYBR green I based closed tube loop mediated isothermal amplification (LAMP) assay and simplified direct-blood-lysis (DBL)-LAMP assay for diagnosis of visceral leishmaniasis (VL). PLoS Negl. Trop. Dis. 2018 12 11 0006922 10.1371/journal.pntd.0006922 30439953
    [Google Scholar]
  25. Abeijon C. Campos-Neto A. Potential non-invasive urine-based antigen (protein) detection assay to diagnose active visceral leishmaniasis. PLoS Negl. Trop. Dis. 2013 7 5 e2161 10.1371/journal.pntd.0002161 23738023
    [Google Scholar]
  26. Jain K. Jain N.K. Vaccines for visceral leishmaniasis: A review. J. Immunol. Methods 2015 422 1 12 10.1016/j.jim.2015.03.017 25858230
    [Google Scholar]
  27. Bhargava P. Singh R. Developments in diagnosis and antileishmanial drugs. Interdiscip. Perspect. Infect. Dis. 2012 2012 1 13 10.1155/2012/626838 23118748
    [Google Scholar]
  28. Selvapandiyan A. Croft S.L. Rijal S. Nakhasi H.L. Ganguly N.K. Innovations for the elimination and control of visceral leishmaniasis. PLoS Negl. Trop. Dis. 2019 13 9 0007616 10.1371/journal.pntd.0007616 31536490
    [Google Scholar]
  29. Osman M. Mistry A. Keding A. A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH. PLoS Negl. Trop. Dis. 2017 11 5 0005527 10.1371/journal.pntd.0005527 28498840
    [Google Scholar]
  30. Das S. Freier A. Boussoffara T. Modular multiantigen T cell epitope-enriched DNA vaccine against human leishmaniasis. Sci. Transl. Med. 2014 6 234 234ra56 10.1126/scitranslmed.3008222 24786324
    [Google Scholar]
  31. Gütschow M. Vanden Eynde J.J. Jampilek J. Breakthroughs in medicinal chemistry: New targets and mechanisms, new drugs, new hopes-7. Molecules 2020 25 13 2968 10.3390/molecules25132968 32605268
    [Google Scholar]
  32. Jones S.T. Cagno V. Janeček M. Modified cyclodextrins as broad-spectrum antivirals. Sci. Adv. 2020 6 5 eaax9318 10.1126/sciadv.aax9318 32064341
    [Google Scholar]
  33. Angeli A. Etxebeste-Mitxeltorena M. Sanmartín C. Tellurides bearing sulfonamides as novel inhibitors of leishmanial carbonic anhydrase with potent antileishmanial activity. J. Med. Chem. 2020 63 8 4306 4314 10.1021/acs.jmedchem.0c00211 32223141
    [Google Scholar]
  34. Mishra S Parmar N Chandrakar P Design, synthesis, in vitro and in vivo biological evaluation of pyranone-piperazine analogs as potent antileishmanial agents. Eur J Med Chem 2021 221 113516-, 1-113516, 14. 10.1016/j.ejmech.2021.113516 33992928
    [Google Scholar]
  35. Nóbrega F.R. Silva L.V. Bezerra Filho C.S.M. Design, antileishmanial activity, and QSAR studies of a series of piplartine analogues. J. Chem. 2019 2019 1 12 10.1155/2019/4785756
    [Google Scholar]
  36. de Oliveira R.G. Cruz L.R. Mollo M.C. Dias L.C. Kratz J.M. Chagas disease drug discovery in Latin America—A mini review of antiparasitic agents explored between 2010 and 2021. Front Chem. 2021 9 771143 10.3389/fchem.2021.771143 34778217
    [Google Scholar]
  37. Satyanarayanajois S.D. Hill R.A. Medicinal Chemistry for 2020. Future Med. Chem. 2011 3 14 1765 1786 10.4155/fmc.11.135 22004084
    [Google Scholar]
  38. Mowbray C.E. Braillard S. Glossop P.A. DNDI-6148: A novel benzoxaborole preclinical candidate for the treatment of Visceral Leishmaniasis. J. Med. Chem. 2021 64 21 16159 16176 10.1021/acs.jmedchem.1c01437 34711050
    [Google Scholar]
  39. Bazin M.A. Cojean S. Pagniez F. In vitro identification of imidazo[1,2-a]pyrazine-based antileishmanial agents and evaluation of L. major casein kinase 1 inhibition. Eur. J. Med. Chem. 2021 210 112956 10.1016/j.ejmech.2020.112956 33148491
    [Google Scholar]
  40. Reguera R.M. Pérez-Pertejo Y. Gutiérrez-Corbo C. Current and promising novel drug candidates against visceral leishmaniasis. Pure Appl. Chem. 2019 91 8 1385 1404 10.1515/pac‑2018‑1102
    [Google Scholar]
  41. Gros L. Castillo-Acosta V.M. Jiménez C.J. New azasterols against Trypanosoma brucei: Role of 24-sterol methyltransferase in inhibitor action. Antimicrob. Agents Chemother. 2006 50 8 2595 2601 10.1128/AAC.01508‑05 16870747
    [Google Scholar]
  42. Gigante F. Kaiser M. Brun R. Gilbert I.H. SAR studies on azasterols as potential anti-trypanosomal and anti-leishmanial agents. Bioorg. Med. Chem. 2009 17 16 5950 5961 10.1016/j.bmc.2009.06.062 19620005
    [Google Scholar]
  43. Orenes Lorente S. Rodrigues J.C.F. Jiménez Jiménez C. Novel azasterols as potential agents for treatment of leishmaniasis and trypanosomiasis. Antimicrob. Agents Chemother. 2004 48 8 2937 2950 10.1128/AAC.48.8.2937‑2950.2004 15273104
    [Google Scholar]
  44. De Rycker M. Wyllie S. Horn D. Read K.D. Gilbert I.H. Anti-trypanosomatid drug discovery: Progress and challenges. Nat. Rev. Microbiol. 2023 21 1 35 50 10.1038/s41579‑022‑00777‑y 35995950
    [Google Scholar]
  45. Bell A.S. Mills J.E. Williams G.P. Selective inhibitors of protozoan protein N-myristoyltransferases as starting points for tropical disease medicinal chemistry programs. PLoS Negl. Trop. Dis. 2012 6 4 e1625 10.1371/journal.pntd.0001625 22545171
    [Google Scholar]
  46. Brannigan J.A. Wilkinson A.J. Drug discovery in leishmaniasis using protein lipidation as a target. Biophys. Rev. 2021 13 6 1139 1146 10.1007/s12551‑021‑00855‑0 35035594
    [Google Scholar]
  47. Durieu E. Prina E. Leclercq O. From drug screening to target deconvolution: A target-based drug discovery pipeline using Leishmania casein kinase 1 isoform 2 to identify compounds with antileishmanial activity. Antimicrob. Agents Chemother. 2016 60 5 2822 2833 10.1128/AAC.00021‑16 26902771
    [Google Scholar]
  48. Moffat J.G. Vincent F. Lee J.A. Eder J. Prunotto M. Opportunities and challenges in phenotypic drug discovery: An industry perspective. Nat. Rev. Drug Discov. 2017 16 8 531 543 10.1038/nrd.2017.111 28685762
    [Google Scholar]
  49. Wheeler N.J. Ryan K.T. Gallo K.J. Multivariate chemogenomic screening prioritizes new macrofilaricidal leads. Commun. Biol. 2023 6 1 44 10.1038/s42003‑023‑04435‑8 36639423
    [Google Scholar]
  50. Choi T.Y. Kim J.H. Ko D.H. Zebrafish as a new model for phenotype‐based screening of melanogenic regulatory compounds. Pigment Cell Res. 2007 20 2 120 127 10.1111/j.1600‑0749.2007.00365.x 17371438
    [Google Scholar]
  51. Ortiz D. Guiguemde W.A. Hammill J.T. Discovery of novel, orally bioavailable, antileishmanial compounds using phenotypic screening. PLoS Negl. Trop. Dis. 2017 11 12 0006157 10.1371/journal.pntd.0006157 29287089
    [Google Scholar]
  52. Mbekeani A.J. Jones R.S. Bassas Llorens M. Mining for natural product antileishmanials in a fungal extract library. Int. J. Parasitol. Drugs Drug Resist. 2019 11 May 118 128 10.1016/j.ijpddr.2019.05.003 31208892
    [Google Scholar]
  53. Wyllie S. Patterson S. Stojanovski L. The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Sci. Transl. Med. 2012 4 119 119re1 10.1126/scitranslmed.3003326 22301556
    [Google Scholar]
  54. Swamy K.C.K. Kumar N.N.B. Balaraman E. Kumar K.V.P.P. Mitsunobu and related reactions: Advances and applications. Chem. Rev. 2009 109 6 2551 2651 10.1021/cr800278z 19382806
    [Google Scholar]
  55. Linciano P. Pozzi C. Iacono L. Enhancement of benzothiazoles as pteridine Reductase-1 inhibitors for the treatment of trypanosomatidic infections. J. Med. Chem. 2019 62 8 3989 4012 10.1021/acs.jmedchem.8b02021 30908048
    [Google Scholar]
  56. Linciano P. Dawson A. Pöhner I. Exploiting the 2-Amino-1,3,4-thiadiazole scaffold to inhibit trypanosoma brucei pteridine reductase in support of early-stage drug discovery. ACS Omega 2017 2 9 5666 5683 10.1021/acsomega.7b00473 28983525
    [Google Scholar]
  57. Coimbra ES Antinarelli LMR de Oliveira Lemos AS da Silva Neto AF Pinheiro AC de Souza MVN Synthesis, biological evaluation and mechanism of action of benzothiazole derivatives with aromatic hydrazone moiety, a new class of antileishmanial compounds. Chem Biol Drug Des 2024 104 1 e14585-, 1-e14585, 11. 10.1111/cbdd.14585 39013834
    [Google Scholar]
  58. Cavassin F.B. Baú-Carneiro J.L. Vilas-Boas R.R. Queiroz-Telles F. Sixty years of Amphotericin B: An overview of the main antifungal agent used to treat invasive fungal infections. Infect. Dis. Ther. 2021 10 1 115 147 10.1007/s40121‑020‑00382‑7 33523419
    [Google Scholar]
  59. Pountain A.W. Weidt S.K. Regnault C. Genomic instability at the locus of sterol C24-methyltransferase promotes amphotericin B resistance in Leishmania parasites. PLoS Negl. Trop. Dis. 2019 13 2 0007052 10.1371/journal.pntd.0007052 30716073
    [Google Scholar]
  60. Charlton R.L. Rossi-Bergmann B. Denny P.W. Steel P.G. Repurposing as a strategy for the discovery of new anti-leishmanials: The-state-of-the-art. Parasitology 2018 145 2 219 236 10.1017/S0031182017000993 28805165
    [Google Scholar]
  61. Phan T.N. Baek K.H. Lee N. Byun S.Y. Shum D. No J.H. In vitro and in vivo activity of mTOR Kinase and PI3K inhibitors against Leishmania donovani and Trypanosoma brucei. Molecules 2020 25 8 1980 10.3390/molecules25081980 32340370
    [Google Scholar]
  62. Zhang H. Yan R. Liu Y. Progress in antileishmanial drugs: Mechanisms, challenges, and prospects. PLoS Negl. Trop. Dis. 2025 19 1 e0012735 10.1371/journal.pntd.0012735 39752369
    [Google Scholar]
  63. Oboh E. Schubert T.J. Teixeira J.E. Optimization of the urea linker of triazolopyridazine mmv665917 results in a new anticryptosporidial lead with improved potency and predicted hERG safety margin. J. Med. Chem. 2021 64 15 11729 11745 10.1021/acs.jmedchem.1c01136 34342443
    [Google Scholar]
  64. Atack JR. GABA (A) receptor subtype-selective efficacy: TPA023, an α2/α3 selective non-sedating anxiolytic and α5IA, an α5 selective cognition enhancer. CNS Neurosci. Ther. 2008 14 1 25 35 10.1111/j.1527‑3458.2007.00034.x 18482097
    [Google Scholar]
  65. Maramai S. Benchekroun M. Ward S.E. Atack J.R. Subtype selective γ-Aminobutyric acid type A receptor (GABA A R) modulators acting at the benzodiazepine binding site: An update. J. Med. Chem. 2020 63 7 3425 3446 10.1021/acs.jmedchem.9b01312 31738537
    [Google Scholar]
  66. Tiwari R. Gupta R.P. Singh V.K. Nanotechnology-based strategies in parasitic disease management: From prevention to diagnosis and treatment. ACS Omega 2023 8 45 42014 42027 10.1021/acsomega.3c04587 38024747
    [Google Scholar]
  67. Frézard F. Aguiar M.M.G. Ferreira L.A.M. Liposomal amphotericin B for treatment of Leishmaniasis: From the identification of critical physicochemical attributes to the design of effective topical and oral formulations. Pharmaceutics 2022 15 1 99 10.3390/pharmaceutics15010099 36678729
    [Google Scholar]
  68. Aragão Horoiwa T Cortez M Sauter IP Sugar-based colloidal nanocarriers for topical meglumine antimoniate application to cuta-neous leishmaniasis treatment: Ex vivo cutaneous retention and in vivo evaluation Eur J Pharm Sci 2020 147 105295-, 1-105295, 9. 10.1016/j.ejps.2020.105295 32145429
    [Google Scholar]
  69. Saudagar P. Dubey V.K. Carbon nanotube based betulin formulation shows better efficacy against Leishmania parasite. Parasitol. Int. 2014 63 6 772 776 10.1016/j.parint.2014.07.008 25086374
    [Google Scholar]
  70. Chaubey P. Patel R.R. Mishra B. Development and optimization of curcumin-loaded mannosylated chitosan nanoparticles using response surface methodology in the treatment of visceral leishmaniasis. Expert Opin. Drug Deliv. 2014 11 8 1163 1181 10.1517/17425247.2014.917076 24875148
    [Google Scholar]
  71. Chaubey P. Mishra B. Mudavath S.L. Mannose-conjugated curcumin-chitosan nanoparticles: Efficacy and toxicity assessments against Leishmania donovani. Int. J. Biol. Macromol. 2018 111 109 120 10.1016/j.ijbiomac.2017.12.143 29307805
    [Google Scholar]
  72. Ovais M. Khalil A.T. Raza A. Multifunctional theranostic applications of biocompatible green-synthesized colloidal nanoparticles. Appl. Microbiol. Biotechnol. 2018 102 10 4393 4408 10.1007/s00253‑018‑8928‑2 29594356
    [Google Scholar]
  73. Sumaira M.S. Siddique Afridi M. Salman Hashmi S. Ali G.S. Zia M. Haider Abbasi B. Comparative antileishmanial efficacy of the biosynthesised ZnO NPs from genus Verbena. IET Nanobiotechnol. 2018 12 8 1067 1073 10.1049/iet‑nbt.2018.5076 30964015
    [Google Scholar]
  74. Bessa I.A.A. D’Amato D.L C Souza A.B. Innovating leishmaniasis treatment: A critical chemist’s review of inorganic nanomaterials. ACS Infect. Dis. 2024 10 8 2485 2506 10.1021/acsinfecdis.4c00231 39001837
    [Google Scholar]
  75. Albalawi A.E. Abdel-Shafy S. Khudair Khalaf A. Therapeutic potential of green synthesized copper nanoparticles alone or combined with meglumine antimoniate (Glucantime®) in Cutaneous Leishmaniasis. Nanomaterials (Basel) 2021 11 4 891 10.3390/nano11040891 33807273
    [Google Scholar]
  76. González M.A.C. Gonçalves A.A.M. Ottino J. Vaccination with formulation of nanoparticles loaded with leishmania amazonensis antigens confers protection against experimental visceral leishmaniasis in hamster. Vaccines (Basel) 2023 11 1 111 10.3390/vaccines11010111 36679956
    [Google Scholar]
  77. Schaduangrat N. Lampa S. Simeon S. Gleeson M.P. Spjuth O. Nantasenamat C. Towards reproducible computational drug discovery. J. Cheminform. 2020 12 1 9 10.1186/s13321‑020‑0408‑x 33430992
    [Google Scholar]
  78. Azam S.S. Abro A. Raza S. Saroosh A. Structure and dynamics studies of sterol 24-C-methyltransferase with mechanism based inactivators for the disruption of ergosterol biosynthesis. Mol. Biol. Rep. 2014 41 7 4279 4293 10.1007/s11033‑014‑3299‑y 24574002
    [Google Scholar]
  79. Prieto-Martínez F.D. López-López E. Eurídice Juárez-Mercado K. Medina-Franco J.L. Computational drug design methods—current and future perspectives. Silico Drug Des 2019 3 19 44 10.1016/B978‑0‑12‑816125‑8.00002‑X
    [Google Scholar]
  80. Forli S. Huey R. Pique M.E. Sanner M.F. Goodsell D.S. Olson A.J. Computational protein–ligand docking and virtual drug screening with the AutoDock suite. Nat. Protoc. 2016 11 5 905 919 10.1038/nprot.2016.051 27077332
    [Google Scholar]
  81. Asiedu S.O. Kwofie S.K. Broni E. Wilson M.D. Computational identification of potential anti-inflammatory natural compounds targeting the p38 mitogen-activated protein Kinase (MAPK): Implications for COVID-19-induced cytokine storm. Biomolecules 2021 11 5 653 678 10.3390/biom11050653 33946644
    [Google Scholar]
  82. Pathania S. Singh P.K. Narang R.K. Rawal R.K. Identifying novel putative ERK1/2 inhibitors via hybrid scaffold hopping –FBDD approach. J. Biomol. Struct. Dyn. 2021 39 1 16 10.1080/07391102.2021.1889670 33615999
    [Google Scholar]
  83. Sidhu K.S. Bhangu S.K. Pathak R.K. Yadav I.S. Chhuneja P. Identification of natural lead compounds for leaf rust of Wheat: A molecular docking and simulation study. J. Proteins Proteom. 2020 11 4 283 295 10.1007/s42485‑020‑00048‑5
    [Google Scholar]
  84. Kwofie S. Broni E. Yunus F. Molecular docking simulation studies identifies potential natural product derived-antiwolbachial compounds as filaricides against onchocerciasis. Biomedicines 2021 9 11 1682 10.3390/biomedicines9111682 34829911
    [Google Scholar]
  85. Tabrez S. Rahman F. Ali R. Repurposing of FDA ‐approved drugs as inhibitors of sterol C‐24 methyltransferase of Leishmania donovani to fight against leishmaniasis. Drug Dev. Res. 2021 82 8 1154 1161 10.1002/ddr.21820 33929761
    [Google Scholar]
  86. Barazorda-Ccahuana H.L. Goyzueta-Mamani L.D. Candia-Puma M.A. de Freitas C.S. Tavares G.D.S.V. Lage D.P. in silico-based screening for natural product’s structural analogs as new drugs candidate against leishmaniasis. bioRxiv 2022 10.1101/2022.07.22.501189
    [Google Scholar]
  87. Broni E. Kwofie S.K. Asiedu S.O. Miller W.A. Wilson M.D. A molecular modeling approach to identify potential antileishmanial compounds against the cell division cycle (cdc)-2-related Kinase 12 (CRK12) receptor of Leishmania donovani. Biomolecules 2021 11 3 458 10.3390/biom11030458 33803906
    [Google Scholar]
  88. Rahman F. Tabrez S. Ali R. Virtual screening of natural compounds for potential inhibitors of Sterol C‐24 methyltransferase of Leishmania donovani to overcome leishmaniasis. J. Cell. Biochem. 2021 122 9 1216 1228 10.1002/jcb.29944 33955051
    [Google Scholar]
  89. Lin X. Li X. Lin X. A review on applications of computational methods in drug screening and design. Molecules 2020 25 6 1375 10.3390/molecules25061375 32197324
    [Google Scholar]
  90. Mouchlis V.D. Afantitis A. Serra A. Advances in de novo drug design: From conventional to Machine Learning methods. Int. J. Mol. Sci. 2021 22 4 1676 10.3390/ijms22041676 33562347
    [Google Scholar]
  91. Yu W. Jr A.D.M. Computer-Aided Drug Design Methods. Antibiot. Methods Protoc 2017 1520 85 106 10.1007/978‑1‑4939‑6634‑9
    [Google Scholar]
  92. Dorahy G. Chen J.Z. Balle T. Computer-aided drug design towards new psychotropic and neurological drugs. Molecules 2023 28 3 1324 10.3390/molecules28031324 36770990
    [Google Scholar]
  93. Islam M.A. Pillay T.S. Identification of promising anti-DNA gyrase antibacterial compounds using de novo design, molecular docking and molecular dynamics studies. J. Biomol. Struct. Dyn. 2019 38 6 1 12 10.1080/07391102.2019.1617785 31084271
    [Google Scholar]
  94. Gangwar S. Baig M.S. Shah P. Identification of novel inhibitors of dipeptidylcarboxypeptidase of Leishmania donovani via ligand-based virtual screening and biological evaluation. Chem. Biol. Drug Des. 2012 79 2 149 156 10.1111/j.1747‑0285.2011.01262.x 22014034
    [Google Scholar]
  95. Emmerich C.H. Gamboa L.M. Hofmann M.C.J. Improving target assessment in biomedical research: The GOT-IT recommendations. Nat. Rev. Drug Discov. 2021 20 1 64 81 10.1038/s41573‑020‑0087‑3 33199880
    [Google Scholar]
  96. Chawla B. Madhubala R. Drug targets in Leishmania. J. Parasit. Dis. 2010 34 1 1 13 10.1007/s12639‑010‑0006‑3 21526026
    [Google Scholar]
  97. Sosa E.J. Burguener G. Lanzarotti E. Target-Pathogen: A structural bioinformatic approach to prioritize drug targets in pathogens. Nucleic Acids Res. 2018 46 D1 D413 D418 10.1093/nar/gkx1015 29106651
    [Google Scholar]
  98. Hosen M.I. Tanmoy A.M. Mahbuba D.A. Application of a subtractive genomics approach for in silico identification and characterization of novel drug targets in Mycobacterium tuberculosis F11. Interdiscip. Sci. 2014 6 1 48 56 10.1007/s12539‑014‑0188‑y 24464704
    [Google Scholar]
  99. Padilla C.A. Alvarez M.J. Combariza A.F. Leishmania Proteomics: An in silico perspective. Preprints 2019 1 36 10.20944/preprints201902.0122.v2
    [Google Scholar]
  100. Jain S. Sahu U. Kumar A. Khare P. Metabolic pathways of Leishmania Parasite: Source of pertinent drug targets and potent drug candidates. Pharmaceutics 2022 14 8 1590 10.3390/pharmaceutics14081590 36015216
    [Google Scholar]
  101. Haanstra J.R. Gerding A. Dolga A.M. Targeting pathogen metabolism without collateral damage to the host. Sci. Rep. 2017 7 1 40406 10.1038/srep40406 28084422
    [Google Scholar]
  102. Hong A. Zampieri R.A. Shaw J.J. Floeter-Winter L.M. Laranjeira-Silva M.F. One health approach to Leishmaniases: Understanding the disease dynamics through diagnostic tools. Pathogens 2020 9 10 809 833 10.3390/pathogens9100809 33019713
    [Google Scholar]
  103. Antwi C.A. Amisigo C.M. Adjimani J.P. Gwira T.M. In vitro activity and mode of action of phenolic compounds on Leishmania donovani. PLoS Negl. Trop. Dis. 2019 13 2 0007206 10.1371/journal.pntd.0007206 30802252
    [Google Scholar]
  104. Monzani P.S. Trapani S. Thiemann O.H. Oliva G. Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase. BMC Struct. Biol. 2007 7 1 59 10.1186/1472‑6807‑7‑59 17894860
    [Google Scholar]
  105. Sundar S. Singh B. Emerging therapeutic targets for treatment of leishmaniasis. Expert Opin. Ther. Targets 2018 22 6 467 486 10.1080/14728222.2018.1472241 29718739
    [Google Scholar]
  106. Patel B. Patel D. Parmar K. Chauhan R. Singh D.D. Pappachan A. L. donovani XPRT: Molecular characterization and evaluation of inhibitors. Biochim. Biophys. Acta. Proteins Proteomics 2018 1866 3 426 441 10.1016/j.bbapap.2017.12.002 29233758
    [Google Scholar]
  107. Elmahallawy E.K. Alkhaldi A.A.M. Insights into leishmania molecules and their potential contribution to the virulence of the parasite. Vet. Sci. 2021 8 2 33 10.3390/vetsci8020033 33672776
    [Google Scholar]
  108. Chawla M. Vishwakarma R.A. Alkylacylglycerolipid domain of GPI molecules of Leishmania is responsible for inhibition of PKC-mediated c-fos expression. J. Lipid Res. 2003 44 3 594 600 10.1194/jlr.M200296‑JLR200 12562866
    [Google Scholar]
  109. Garami A. Mehlert A. Ilg T. Glycosylation defects and virulence phenotypes of Leishmania mexicana phosphomannomutase and dolicholphosphate-mannose synthase gene deletion mutants. Mol. Cell. Biol. 2001 21 23 8168 8183 10.1128/MCB.21.23.8168‑8183.2001 11689705
    [Google Scholar]
  110. Colmenares M. Tiemeyer M. Kima P. McMahon-Pratt D. Biochemical and biological characterization of the protective Leishmania pifanoi amastigote antigen P-8. Infect. Immun. 2001 69 11 6776 6784 10.1128/IAI.69.11.6776‑6784.2001 11598050
    [Google Scholar]
  111. Masterson W.J. Ferguson M.A. Phenylmethanesulphonyl fluoride inhibits GPI anchor biosynthesis in the African trypanosome. EMBO J. 1991 10 8 2041 2045 10.1002/j.1460‑2075.1991.tb07734.x 1829674
    [Google Scholar]
  112. de Macedo C.S. Shams-Eldin H. Smith T.K. Schwarz R.T. Azzouz N. Inhibitors of glycosyl-phosphatidylinositol anchor biosynthesis. Biochimie 2003 85 3-4 465 472 10.1016/S0300‑9084(03)00065‑8 12770785
    [Google Scholar]
  113. McDowell W. Schwarz R.T. Specificity of GDP‐Man:dolichyl‐phosphate mannosyltransferase for the guanosine diphosphate esters of mannose analogues containing deoxy and deoxyfluoro substituents. FEBS Lett. 1989 243 2 413 416 10.1016/0014‑5793(89)80173‑5 2917659
    [Google Scholar]
  114. Vickers T.J. Beverley S.M. Folate metabolic pathways in Leishmania. Essays Biochem. 2011 51 63 80 10.1042/bse0510063 22023442
    [Google Scholar]
  115. Bigot S. Leprohon P. Ouellette M. Delving in folate metabolism in the parasite Leishmania major through a chemogenomic screen and methotrexate selection. PLoS Negl. Trop. Dis. 2023 17 6 0011458 10.1371/journal.pntd.0011458 37384801
    [Google Scholar]
  116. Richard D. Kündig C. Ouellette M. A new type of high affinity folic acid transporter in the protozoan parasite Leishmania and deletion of its gene in methotrexate-resistant cells. J. Biol. Chem. 2002 277 33 29460 29467 10.1074/jbc.M204796200 12023977
    [Google Scholar]
  117. Gilbert I.H. Inhibitors of dihydrofolate reductase in leishmania and trypanosomes. Biochim. Biophys. Acta Mol. Basis Dis. 2002 1587 2-3 249 257 10.1016/S0925‑4439(02)00088‑1 12084467
    [Google Scholar]
  118. Pez D. Leal I. Zuccotto F. 2,4-Diaminopyrimidines as inhibitors of Leishmanial and Trypanosomal dihydrofolate reductase. Bioorg. Med. Chem. 2003 11 22 4693 4711 10.1016/j.bmc.2003.08.012 14556785
    [Google Scholar]
  119. Sharma V.K. Bharatam P.V. Identification of selective inhibitors of Ld DHFR enzyme using pharmacoinformatic methods. J. Comput. Biol. 2021 28 1 43 59 10.1089/cmb.2019.0332 32207987
    [Google Scholar]
  120. Bibi M Qureshi NA Sadiq A Exploring the ability of dihydro-pyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase Eur J Med Chem 2021 210 112986-, 1-112986, 46. 10.1016/j.ejmech.2020.112986 33187806
    [Google Scholar]
  121. Ferone R. Dihydrofolate reductase inhibitors. Handbook of Ex-perimental Pharmacology. Berlin, Heidelberg: Springer 1984 68 / 2 207 221 10.1007/978‑3‑642‑69254‑3_5
    [Google Scholar]
  122. Leite F.H.A. Froes T.Q. da Silva S.G. An integrated approach towards the discovery of novel non-nucleoside Leishmania major pteridine reductase 1 inhibitors. Eur. J. Med. Chem. 2017 132 322 332 10.1016/j.ejmech.2017.03.043 28407565
    [Google Scholar]
  123. Tulloch L.B. Martini V.P. Iulek J. Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases. J. Med. Chem. 2010 53 1 221 229 10.1021/jm901059x 19916554
    [Google Scholar]
  124. Shtaiwi A. Thiadiazine-thiones as inhibitors of leishmania pteridine reductase (PTR1) target: Investigations and in silico approach. J. Biomol. Struct. Dyn. 2023 0 0 1 10 10.1080/07391102.2023.2246589 37578348
    [Google Scholar]
  125. Cavazzuti A. Paglietti G. Hunter W.N. Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development. Proc. Natl. Acad. Sci. USA 2008 105 5 1448 1453 10.1073/pnas.0704384105 18245389
    [Google Scholar]
  126. Patil S.R. Asrondkar A. Patil V. Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies. Bioorg. Med. Chem. Lett. 2017 27 16 3845 3850 10.1016/j.bmcl.2017.06.053 28693910
    [Google Scholar]
  127. Temraz M.G. Elzahhar P.A. El-Din A. Bekhit A. Bekhit A.A. Labib H.F. Belal A.S.F. Anti-leishmanial click modifiable thiosemicarbazones: Design, synthesis, biological evaluation and in silico studies. Eur. J. Med. Chem. 2018 151 585 600 10.1016/j.ejmech.2018.04.003 29656201
    [Google Scholar]
  128. Herrmann F. Sivakumar N. Jose J. Costi M. Pozzi C. Schmidt T. In silico identification and in vitro evaluation of natural inhibitors of leishmania major pteridine reductase I. Molecules 2017 22 12 2166 10.3390/molecules22122166 29211037
    [Google Scholar]
  129. Possart K. Herrmann F.C. Jose J. Costi M.P. Schmidt T.J. Sesquiterpene lactones with dual inhibitory activity against the trypanosoma brucei pteridine reductase 1 and dihydrofolate reductase. Molecules 2021 27 1 149 10.3390/molecules27010149 35011381
    [Google Scholar]
  130. Teixeira B.V.F. Teles A.L.B. Silva S.G. Dual and selective inhibitors of pteridine reductase 1 (PTR1) and dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Leishmania chagasi. J. Enzyme Inhib. Med. Chem. 2019 34 1 1439 1450 10.1080/14756366.2019.1651311 31409157
    [Google Scholar]
  131. Romero A.H. Rodríguez N. Oviedo H. 2-Aryl-quinazolin-4(3H)-ones as an inhibitor of leishmania folate pathway: In vitro biological evaluation, mechanism studies and molecular docking. Bioorg. Chem. 2019 83 83 145 153 10.1016/j.bioorg.2018.10.028 30359795
    [Google Scholar]
  132. Mendoza-Martínez C. Galindo-Sevilla N. Correa-Basurto J. Antileishmanial activity of quinazoline derivatives: Synthesis, docking screens, molecular dynamic simulations and electrochemical studies. Eur. J. Med. Chem. 2015 92 314 331 10.1016/j.ejmech.2014.12.051 25576738
    [Google Scholar]
  133. Van Horn K.S. Zhu X. Pandharkar T. Antileishmanial activity of a series of N2,N4-disubstituted quinazoline-2,4-diamines. J. Med. Chem. 2014 57 12 5141 5156 10.1021/jm5000408 24874647
    [Google Scholar]
  134. Kapil S. Singh P.K. Kashyap A. Silakari O. Structure based designing of benzimidazole/benzoxazole derivatives as anti-leishmanial agents. SAR QSAR Environ. Res. 2019 30 12 919 933 10.1080/1062936X.2019.1684357 31702401
    [Google Scholar]
  135. Singh S. Raju K. Jatekar D. Dinesh N. Paul M.S. Sobhia M.E. Leishmania donovani eukaryotic initiation factor 5A: Molecular characterization, localization and homology modelling studies. Microb. Pathog. 2014 73 1 37 46 10.1016/j.micpath.2014.05.005 24909104
    [Google Scholar]
  136. Chawla B. Kumar R.R. Tyagi N. A unique modification of the eukaryotic initiation factor 5A shows the presence of the complete hypusine pathway in Leishmania donovani. PLoS One 2012 7 3 33138 10.1371/journal.pone.0033138 22438895
    [Google Scholar]
  137. Garcia A.R. Oliveira D.M.P. Claudia F. Amaral A. Leishmania infantum arginase: Biochemical characterization and inhibition by naturally occurring phenolic substances. J. Enzyme Inhib. Med. Chem. 2019 34 1 1100 1109 10.1080/14756366.2019.1616182 31124384
    [Google Scholar]
  138. Garcia A.R. Oliveira D.M.P. Jesus J.B. Identification of chalcone derivatives as inhibitors of Leishmania infantum arginase and promising antileishmanial agents. Front Chem. 2021 8 January 624678 10.3389/fchem.2020.624678 33520939
    [Google Scholar]
  139. da Silva E.R. Maquiaveli C.C. Magalhães P.P. The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase. Exp. Parasitol. 2012 130 3 183 188 10.1016/j.exppara.2012.01.015 22327179
    [Google Scholar]
  140. Crizanto de Lima E. Castelo-Branco F.S. Maquiaveli C.C. Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity. Bioorg. Med. Chem. 2019 27 17 3853 3859 10.1016/j.bmc.2019.07.022 31311700
    [Google Scholar]
  141. Sheikh S.Y. Ansari W.A. Hassan F. Drug repositioning to discover novel ornithine decarboxylase inhibitors against visceral leishmaniasis. J. Mol. Recognit. 2023 36 7 3021 10.1002/jmr.3021 37092713
    [Google Scholar]
  142. Scalese G Mosquillo MF Pérez-Díaz L Gambino D Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds. Coord Chem Rev 2024 503 215608-, 1-215608, 28. 10.1016/j.ccr.2023.215608
    [Google Scholar]
  143. Singh S. Babu N.K. 3-Hydroxy-3-Methylglutaryl-CoA reductase (HMGR) enzyme of the sterol biosynthetic pathway: A potential target against visceral Leishmaniasis. IntechOpen 2018 133 141 10.5772/intechopen.75480
    [Google Scholar]
  144. Shokri A. Abastabar M. Keighobadi M. Promising antileishmanial activity of novel imidazole antifungal drug luliconazole against Leishmania major: In vitro and in silico studies. J. Glob. Antimicrob. Resist. 2018 14 260 265 10.1016/j.jgar.2018.05.007 29793051
    [Google Scholar]
  145. Andrade-Neto V.V. Manso P.P.A. Pereira M.G. Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis. Mem. Inst. Oswaldo Cruz 2022 117 220407 10.1590/0074‑02760220407 35384972
    [Google Scholar]
  146. Tulloch L.B. Tinti M. Wall R.J. Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1. PLoS Pathog. 2024 20 7 1012382 10.1371/journal.ppat.1012382 38991025
    [Google Scholar]
  147. Dinc R. Leishmania vaccines: The current situation with its promising aspect for the future. Korean J. Parasitol. 2022 60 6 379 391 10.3347/kjp.2022.60.6.379 36588414
    [Google Scholar]
  148. Montalvetti A. Peña-Díaz J. Hurtado R. Ruiz-Pérez L.M. González-Pacanowska D. Characterization and regulation of Leishmania major 3-hydroxy-3-methylglutaryl-CoA reductase. Biochem. J. 2000 349 Pt 1 27 34 10.1042/bj3490027 10861207
    [Google Scholar]
  149. Dinesh N. Pallerla D.S.R. Kaur P.K. Kishore Babu N. Singh S. Exploring Leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) as a potential drug target by biochemical, biophysical and inhibition studies. Microb. Pathog. 2014 66 14 23 10.1016/j.micpath.2013.11.001 24239940
    [Google Scholar]
  150. Ortiz-Gómez A. Jiménez C. Estévez A.M. Carrero-Lérida J. Ruiz-Pérez L.M. González-Pacanowska D. Farnesyl diphosphate synthase is a cytosolic enzyme in Leishmania major promastigotes and its overexpression confers resistance to risedronate. Eukaryot. Cell 2006 5 7 1057 1064 10.1128/EC.00034‑06 16835450
    [Google Scholar]
  151. Ribeiro JM Rodrigues-Alves ML Oliveira E Pamidronate, a promising repositioning drug to treat leishmaniasis, displays antileishmanial and immunomodulatory potential. Int Immunopharma-col 2022 110 108952-, 1-108952, 12. 10.1016/j.intimp.2022.108952 35716482
    [Google Scholar]
  152. Gadelha A.P.R. Brigagao C.M. da Silva M.B. Insights about the structure of farnesyl diphosphate synthase (FPPS) and the activity of bisphosphonates on the proliferation and ultrastructure of Leishmania and Giardia. Parasit. Vectors 2020 13 1 168 10.1186/s13071‑020‑04019‑z 32248823
    [Google Scholar]
  153. Urbina J.A. Concepcion J.L. Rangel S. Visbal G. Lira R. Squalene synthase as a chemotherapeutic target in Trypanosoma cruzi and Leishmania mexicana. Mol. Biochem. Parasitol. 2002 125 1-2 35 45 10.1016/S0166‑6851(02)00206‑2 12467972
    [Google Scholar]
  154. Wadanambi PM Mannapperuma U Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase from Leishmania donovani. Heliyon 2021 7 6 e07178-, 1-e07178, 14. 10.1016/j.heliyon.2021.e07178 34141935
    [Google Scholar]
  155. de Macedo-Silva S.T. Visbal G. Souza G.F. Benzylamines as highly potent inhibitors of the sterol biosynthesis pathway in Leishmania amazonensis leading to oxidative stress and ultrastructural alterations. Sci. Rep. 2022 12 1 11313 10.1038/s41598‑022‑15449‑3 35788652
    [Google Scholar]
  156. Granthon A.C. Braga M.V. Rodrigues J.C.F. Alterations on the growth and ultrastructure of Leishmania chagasi induced by squalene synthase inhibitors. Vet. Parasitol. 2007 146 1-2 25 34 10.1016/j.vetpar.2006.12.022 17367936
    [Google Scholar]
  157. Fernandes Rodrigues J.C. Concepcion J.L. Rodrigues C. Caldera A. Urbina J.A. de Souza W. In vitro activities of ER-119884 and E5700, two potent squalene synthase inhibitors, against Leishmania amazonensis: Antiproliferative, biochemical, and ultrastructural effects. Antimicrob. Agents Chemother. 2008 52 11 4098 4114 10.1128/AAC.01616‑07 18765694
    [Google Scholar]
  158. de Souza W. Rodrigues J.C.F. Sterol biosynthesis pathway as target for anti-trypanosomatid drugs. Interdiscip. Perspect. Infect. Dis. 2009 2009 1 19 10.1155/2009/642502 19680554
    [Google Scholar]
  159. Kaneshiro E.S. Collins M.S. Cushion M.T. Inhibitors of sterol biosynthesis and amphotericin B reduce the viability of pneumocystis carinii f. sp. carinii. Antimicrob. Agents Chemother. 2000 44 6 1630 1638 10.1128/AAC.44.6.1630‑1638.2000 10817720
    [Google Scholar]
  160. Beach D.H. Goad L.J. Berman J.D. Ellenberger T.E. Beverley S.M. Holz G.G. Effects of a Squalene-2,3-epoxidase inhibitor on propagation and sterol biosynthesis of leishmania promastigotes and amastigotes. Leishmaniasis 1989 885 890 10.1007/978‑1‑4613‑1575‑9_111
    [Google Scholar]
  161. Ray S. Das S. Suar M. Molecular mechanism of drug resistance. Resistance in Bacteria, Fungi, Malaria, and Cancer. Cham Springer 2017 47 110 10.1007/978‑3‑319‑48683‑3_3
    [Google Scholar]
  162. Nowosielski M. Hoffmann M. Wyrwicz L.S. Detailed mechanism of squalene epoxidase inhibition by terbinafine. J. Chem. Inf. Model. 2011 51 2 455 462 10.1021/ci100403b 21229992
    [Google Scholar]
  163. Bezerra-Souza A. Yamamoto E.S. Laurenti M.D. Ribeiro S.P. Passero L.F.D. Passero F.D. The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis. Parasitol. Int. 2016 65 6 702 707 10.1016/j.parint.2016.08.003 27546158
    [Google Scholar]
  164. Leañez J. Nuñez J. García-Marchan Y. Anti-leishmanial effect of spiro dihydroquinoline-oxindoles on volume regulation decrease and sterol biosynthesis of Leishmania braziliensis. Exp. Parasitol. 2019 198 31 38 10.1016/j.exppara.2019.01.011 30690024
    [Google Scholar]
  165. Berman J.D. Gallalee J.V. Therapeutics E. Reed W. In vitro antileishmanial activity of inhibitors of steroid biosynthesis and combinations of antileishmanial agents. J. Parasitol. 1987 73 3 671 673 3037057
    [Google Scholar]
  166. McCall L.I. El Aroussi A. Choi J.Y. Targeting Ergosterol biosynthesis in Leishmania donovani: Essentiality of sterol 14 alpha-demethylase. PLoS Negl. Trop. Dis. 2015 9 3 0003588 10.1371/journal.pntd.0003588 25768284
    [Google Scholar]
  167. Lepesheva G.I. Waterman M.R. Sterol 14alpha-demethylase (CYP51) as a therapeutic target for human trypanosomiasis and leishmaniasis. Curr. Top. Med. Chem. 2011 11 16 2060 2071 10.2174/156802611796575902 21619513
    [Google Scholar]
  168. Baek K.H. Phan T.N. Malwal S.R. In vivo efficacy of SQ109 against Leishmania donovani, Trypanosoma spp. and Toxoplasma gondii and in vitro activity of SQ109 Metabolites. Biomedicines 2022 10 3 670 10.3390/biomedicines10030670 35327472
    [Google Scholar]
  169. Bhandari K. Srinivas N. Marrapu V.K. Verma A. Srivastava S. Gupta S. Synthesis of substituted aryloxy alkyl and aryloxy aryl alkyl imidazoles as antileishmanial agents. Bioorg. Med. Chem. Lett. 2010 20 1 291 293 10.1016/j.bmcl.2009.10.117 19913413
    [Google Scholar]
  170. de Macedo-Silva ST Urbina JA de Souza W Rodrigues JCF In vitro activity of the antifungal azoles itraconazole and posaconazole against Leishmania amazonensis PLoS One 2013 8 12 e83247-, 1-e83247, 14. 10.1371/journal.pone.0083247 24376670
    [Google Scholar]
  171. Barrett M.P. Croft S.L. Management of trypanosomiasis and leishmaniasis. Br. Med. Bull. 2012 104 1 175 196 10.1093/bmb/lds031 23137768
    [Google Scholar]
  172. Abdelhameed A. Feng M. Joice A.C. Synthesis and antileishmanial evaluation of Arylimidamide–Azole hybrids containing a Phenoxyalkyl linker. ACS Infect. Dis. 2021 7 7 1901 1922 10.1021/acsinfecdis.0c00855 33538576
    [Google Scholar]
  173. Mukherjee S. Xu W. Hsu F.F. Patel J. Huang J. Zhang K. Sterol methyltransferase is required for optimal mitochondrial function and virulence in Leishmania major. Mol. Microbiol. 2019 111 1 65 81 10.1111/mmi.14139 30260041
    [Google Scholar]
  174. Yamamoto ES de Jesus JA Bezerra-Souza A Tolnaftate inhibits ergosterol production and impacts cell viability of Leishmania sp. Bioorg Chem 2020 102 104056-, 1-104056, 8. 10.1016/j.bioorg.2020.104056 32653607
    [Google Scholar]
  175. Khan H. Waqas M. Khurshid B. Ullah N. Khalid A. Abdalla A.N. Investigating the role of Sterol C24-Methyl transferase mutation on drug resistance in leishmaniasis and identifying potential inhibitors. J. Biomol. Struct. Dyn. 2023 42 19 10374 10387 10.1080/07391102.2023.2256879 37723868
    [Google Scholar]
  176. Magaraci F. Jimenez C.J. Rodrigues C. Azasterols as inhibitors of sterol 24-methyltransferase in Leishmania species and Trypanosoma cruzi. J. Med. Chem. 2003 46 22 4714 4727 10.1021/jm021114j 14561091
    [Google Scholar]
  177. Kumari D Kour P Singh CP Anhydroparthenin as a dual-tar-get inhibitor against Sterol C-24 methyltransferase and Sterol 14-α demethylase of Leishmania donovani: A comprehensive in vitro and in silico study. Int J Biol Macromol 2024 269 Pt 1 132034-, 1-132034, 17. 10.1016/j.ijbiomac.2024.132034 38702006
    [Google Scholar]
  178. Pawłowska M. Mila-Kierzenkowska C. Szczegielniak J. Woźniak A. Oxidative stress in parasitic diseases—Reactive oxygen species as mediators of interactions between the host and the parasites. Antioxidants 2023 13 1 38 10.3390/antiox13010038 38247462
    [Google Scholar]
  179. Reverte M. Eren R.O. Jha B. The antioxidant response favors Leishmania parasites survival, limits inflammation and reprograms the host cell metabolism. PLoS Pathog. 2021 17 3 1009422 10.1371/journal.ppat.1009422 33765083
    [Google Scholar]
  180. Prakash J. Yadav S. Saha G. Episomal expression of human glutathione reductase (HuGR) in Leishmania sheds light on evolutionary pressure for unique redox metabolism pathway: Impaired stress tolerance ability of Leishmania donovani. Int. J. Biol. Macromol. 2019 121 498 507 10.1016/j.ijbiomac.2018.10.036 30316767
    [Google Scholar]
  181. Ali V. Behera S. Nawaz A. Equbal A. Pandey K. Unique thiol metabolism in trypanosomatids: Redox homeostasis and drug resistance. Adv. Parasitol. 2022 117 75 155 10.1016/bs.apar.2022.04.002 35878950
    [Google Scholar]
  182. Battista T. Colotti G. Ilari A. Fiorillo A. Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases. Molecules 2020 25 8 1924 10.3390/molecules25081924 32326257
    [Google Scholar]
  183. Turcano L. Torrente E. Missineo A. Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening. PLoS Negl. Trop. Dis. 2018 12 11 0006969 10.1371/journal.pntd.0006969 30475811
    [Google Scholar]
  184. Irigoín F. Cibils L. Comini M.A. Wilkinson S.R. Flohé L. Radi R. Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification. Free Radic. Biol. Med. 2008 45 6 733 742 10.1016/j.freeradbiomed.2008.05.028 18588970
    [Google Scholar]
  185. Kikowska M. Chanaj-Kaczmarek J. Derda M. The evaluation of phenolic acids and flavonoids content and antiprotozoal activity of Eryngium species biomass produced by biotechnological methods. Molecules 2022 27 2 363 10.3390/molecules27020363 35056679
    [Google Scholar]
  186. Inacio JDF Fonseca MS Limaverde-Sousa G Tomas AM Castro H Almeida-Amaral EE Epigallocathechin-O-3-Gallate inhibits trypanothione reductase of Leishmania infantum, causing alterations in redox balance and leading to parasite death. Front Cell Infect Mi-crobiol 2021 11 640561-, 1-640561, 11. 10.3389/fcimb.2021.640561 33842389
    [Google Scholar]
  187. Sharma N. Shukla A.K. Das M. Dubey V.K. Evaluation of plumbagin and its derivative as potential modulators of redox thiol metabolism of Leishmania parasite. Parasitol. Res. 2012 110 1 341 348 10.1007/s00436‑011‑2498‑x 21717278
    [Google Scholar]
  188. Ilari A. Baiocco P. Messori L. A gold-containing drug against parasitic polyamine metabolism: The X-ray structure of trypanothione reductase from Leishmania infantum in complex with auranofin reveals a dual mechanism of enzyme inhibition. Amino Acids 2012 42 2-3 803 811 10.1007/s00726‑011‑0997‑9 21833767
    [Google Scholar]
  189. Schirmann J.G. Bortoleti B.T.S. Gonçalves M.D. In-vitro biological evaluation of 3,3′,5,5′-tetramethoxy-biphenyl-4,4′-diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti-leishmania potential. Sci. Rep. 2023 13 1 6928 10.1038/s41598‑023‑34124‑9 37117253
    [Google Scholar]
  190. Madia V.N. Ialongo D. Patacchini E. Inhibition of Leishmania infantum trypanothione reductase by new aminopropanone derivatives interacting with the NADPH binding site. Molecules 2023 28 1 338 10.3390/molecules28010338 36615531
    [Google Scholar]
  191. Alcón-Calderón M de Lucio H García-Soriano JC Identifica-tion of L. infantum trypanothione synthetase inhibitors with leish-manicidal activity from a (non-biased) in-house chemical library Eur J Med Chem 2022 243 114675-, 1-114675, 14. 10.1016/j.ejmech.2022.114675 36075146
    [Google Scholar]
  192. Saudagar P. Dubey V.K. Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani. Biol. Chem. 2011 392 12 1113 1122 10.1515/BC.2011.222 22050226
    [Google Scholar]
  193. Nateghi-Rostami M Tasbihi M Darzi F Involvement of try-paredoxin peroxidase (TryP) and trypanothione reductase (TryR) in antimony unresponsive of Leishmania tropica clinical isolates of Iran Acta Trop 2022 230 106392-, 1-106392, 8. 10.1016/j.actatropica.2022.106392 35276060
    [Google Scholar]
  194. Wyllie S. Mandal G. Singh N. Sundar S. Fairlamb A.H. Chatterjee M. Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates. Mol. Biochem. Parasitol. 2010 173 2 162 164 10.1016/j.molbiopara.2010.05.015 20553768
    [Google Scholar]
  195. Gundampati R.K. Sahu S. Srivastava A.K. Chandrasekaran S. Vuddanda P.R. Pandey R.K. In silico and in vitro studies: Tryparedoxin peroxidase inhibitor activity of methotrexate for antileishmanial activity. Am. J. Infect. Dis. 2013 9 4 117 129 10.3844/ajidsp.2013.117.129
    [Google Scholar]
  196. Brindisi M. Brogi S. Relitti N. Structure-based discovery of the first non-covalent inhibitors of Leishmania major tryparedoxin peroxidase by high throughput docking. Sci. Rep. 2015 5 1 9705 10.1038/srep09705 25951439
    [Google Scholar]
  197. Ohms M Ferreira C Busch H Enhanced glycolysis is required for antileishmanial functions of neutrophils upon infection With Leishmania donovani. Front Immunol 2021 12 632512-, 1-632512, 14. 10.3389/fimmu.2021.632512 33815385
    [Google Scholar]
  198. McConville MJ Saunders EC Kloehn J Dagley MJ Leishmania carbon metabolism in the macrophage phagolysosome- Feast or fam-ine? F1000 Res 2015 4 F1000 Faculty Rev 938 949 10.12688/f1000research.6724.1 26594352
    [Google Scholar]
  199. Rodriguez-Contreras D. Hamilton N. Gluconeogenesis in Leishmania mexicana. J. Biol. Chem. 2014 289 47 32989 33000 10.1074/jbc.M114.569434 25288791
    [Google Scholar]
  200. Saunders E.C. De Souza D.P. Naderer T. Central carbon metabolism of Leishmania parasites. Parasitology 2010 137 9 1303 1313 10.1017/S0031182010000077 20158936
    [Google Scholar]
  201. Raj S. Sasidharan S. Balaji S.N. Saudagar P. An overview of biochemically characterized drug targets in metabolic pathways of Leishmania parasite. Parasitol. Res. 2020 119 7 2025 2037 10.1007/s00436‑020‑06736‑x 32504119
    [Google Scholar]
  202. Tanner L.B. Goglia A.G. Wei M.H. Four key steps control glycolytic flux in mammalian cells. Cell Syst. 2018 7 1 49 62.e8 10.1016/j.cels.2018.06.003 29960885
    [Google Scholar]
  203. Gabaldón T. Ginger M.L. Michels P.A.M. Peroxisomes in parasitic protists. Mol. Biochem. Parasitol. 2016 209 1-2 35 45 10.1016/j.molbiopara.2016.02.005 26896770
    [Google Scholar]
  204. Rigden D.J. Phillips S.E.V. Michels P.A.M. Fothergill-Gilmore L.A. The structure of pyruvate kinase from Leishmania mexicana reveals de-tails of the allosteric transition and unusual effector specificity 1 1Ed-ited by I. A. Wilson. J Mol Biol 1999 291 3 615 635 10.1006/jmbi.1999.2918 10448041
    [Google Scholar]
  205. Yousef B.A. Elwaseela T.H. Ali T.A. Anti-malarial drugs as potential inhibitors of leishmania glycolytic enzymes: Development of new anti-leishmanial agents. Pharmacol Clin Pharm Res 2020 5 3 77 88 10.15416/pcpr.v5i3.29380
    [Google Scholar]
  206. Amiri-Dashatan N. Rezaei-Tavirani M. Ranjbar M.M. Koushki M. Mousavi Nasab S.D. Ahmadi N. Discovery of novel pyruvate kinase inhibitors against Leishmania major among FDA approved drugs through system biology and molecular docking approach. Turk. J. Pharm. Sci. 2021 18 6 710 717 10.4274/tjps.galenos.2021.53367 34978400
    [Google Scholar]
  207. Khanra S. Juin S.K. Jawed J.J. In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. PLoS Negl. Trop. Dis. 2020 14 8 0008575 10.1371/journal.pntd.0008575 32866156
    [Google Scholar]
  208. Prada C.F. Álvarez-Velilla R. Balaña-Fouce R. Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect. Biochem. Pharmacol. 2013 85 10 1433 1440 10.1016/j.bcp.2013.02.024 23466420
    [Google Scholar]
  209. Hazra S. Ghosh S. Sarma M.D. Evaluation of a diospyrin derivative as antileishmanial agent and potential modulator of ornithine decarboxylase of Leishmania donovani. Exp. Parasitol. 2013 135 2 407 413 10.1016/j.exppara.2013.07.021 23973194
    [Google Scholar]
  210. Ray S. Hazra B. Mittra B. Das A. Majumder H.K. Diospyrin, a bisnaphthoquinone: A novel inhibitor of type I DNA topoisomerase of Leishmania donovani. Mol. Pharmacol. 1998 54 6 994 999 10.1124/mol.54.6.994 9855627
    [Google Scholar]
  211. Velásquez A.M.A. Ribeiro W.C. Venn V. Efficacy of a binuclear cyclopalladated compound therapy for cutaneous leishmaniasis in the murine model of infection with leishmania amazonensis and its inhibitory effect on Topoisomerase 1B. Antimicrob. Agents Chemother. 2017 61 8 e00688 e17 10.1128/AAC.00688‑17 28507113
    [Google Scholar]
  212. Carballeira N.M. Cartagena M. Sanabria D. 2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani. Bioorg. Med. Chem. Lett. 2012 22 19 6185 6189 10.1016/j.bmcl.2012.08.019 22932312
    [Google Scholar]
  213. Chowdhury S.R. Godinho J.L.P. Vinayagam J. Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II, disrupts mitochondrial architecture in trypanosomatid parasites. Sci. Rep. 2018 8 1 11940 10.1038/s41598‑018‑30405‑w 30093616
    [Google Scholar]
  214. Cortázar T.M. Coombs G.H. Walker J. Leishmania panamensis: Comparative inhibition of nuclear DNA topoisomerase II enzymes from promastigotes and human macrophages reveals anti-parasite selectivity of fluoroquinolones, flavonoids and pentamidine. Exp. Parasitol. 2007 116 4 475 482 10.1016/j.exppara.2007.02.018 17466980
    [Google Scholar]
  215. Efstathiou A. Smirlis D. Leishmania Protein Kinases: Important regulators of the parasite life cycle and molecular targets for treating leishmaniasis. Microorganisms 2021 9 4 691 10.3390/microorganisms9040691 33801655
    [Google Scholar]
  216. Baker N. Catta-Preta C.M.C. Neish R. Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival. Nat. Commun. 2021 12 1 1244 10.1038/s41467‑021‑21360‑8 33623024
    [Google Scholar]
  217. Bhattacharjee A Bagchi A Sarkar S Bawali S Bhattacharya A Biswas A Repurposing approved protein kinase inhibitors as potent anti-leishmanials targeting Leishmania MAP kinases. Life Sci 2024 351 122844-, 1-122844, 17. 10.1016/j.lfs.2024.122844 38897344
    [Google Scholar]
  218. Raj S. Saha G. Sasidharan S. Dubey V.K. Saudagar P. Biochemical characterization and chemical validation of Leishmania MAP Kinase-3 as a potential drug target. Sci. Rep. 2019 9 1 16209 10.1038/s41598‑019‑52774‑6 31700105
    [Google Scholar]
  219. Ochoa R. Ortega-Pajares A. Castello F.A. Identification of potential kinase inhibitors within the PI3K/AKT pathway of Leishmania species. Biomolecules 2021 11 7 1037 10.3390/biom11071037 34356660
    [Google Scholar]
  220. Cleghorn L.A.T. Woodland A. Collie I.T. Identification of inhibitors of the Leishmania cdc2-related protein kinase CRK3. ChemMedChem 2011 6 12 2214 2224 10.1002/cmdc.201100344 21913331
    [Google Scholar]
  221. Alves C.R. Souza R.S. Charret K.S. Understanding serine proteases implications on Leishmania spp lifecycle. Exp. Parasitol. 2018 184 67 81 10.1016/j.exppara.2017.11.008 29175018
    [Google Scholar]
  222. Gupta A.K. Das S. Kamran M. Ejazi S.A. Ali N. The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses. Virulence 2022 13 1 903 935 10.1080/21505594.2022.2074130 35531875
    [Google Scholar]
  223. Mahmoudzadeh-Niknam H. McKerrow J.H. Leishmania tropica: Cysteine proteases are essential for growth and pathogenicity. Exp. Parasitol. 2004 106 3-4 158 163 10.1016/j.exppara.2004.03.005 15172223
    [Google Scholar]
  224. Gupta G. Oghumu S. Satoskar A.R. Mechanisms of immune evasion in leishmaniasis. Adv. Appl. Microbiol. 2013 82 155 184 10.1016/B978‑0‑12‑407679‑2.00005‑3 23415155
    [Google Scholar]
  225. Isnard A. Shio M.T. Olivier M. Impact of Leishmania metalloprotease GP63 on macrophage signaling. Front. Cell. Infect. Microbiol. 2012 2 72 81 10.3389/fcimb.2012.00072 22919663
    [Google Scholar]
  226. Paik D. Das P. De T. Chakraborti T. In vitro anti-leishmanial efficacy of potato tuber extract (PTEx): Leishmanial serine protease(s) as putative target. Exp. Parasitol. 2014 146 11 19 10.1016/j.exppara.2014.08.009 25128800
    [Google Scholar]
  227. Souza-Silva F. Bourguignon S.C. Pereira B.A.S. Epoxy-α-lapachone has in vitro and in vivo anti-leishmania (Leishmania) amazonensis effects and inhibits serine proteinase activity in this parasite. Antimicrob. Agents Chemother. 2015 59 4 1910 1918 10.1128/AAC.04742‑14 25583728
    [Google Scholar]
  228. Pereira I.O. Assis D.M. Juliano M.A. Natural products from Garcinia brasiliensis as Leishmania protease inhibitors. J. Med. Food 2011 14 6 557 562 10.1089/jmf.2010.0018 21554130
    [Google Scholar]
  229. Sharma S. Anjaneyulu Yakkala P. Beg M.A. 5‐Arylidene‐2,4‐thiazolidinediones as Cysteine Protease Inhibitors against Leishmania Donovani. ChemistrySelect 2023 8 29 202302415 10.1002/slct.202302415
    [Google Scholar]
  230. Steert K. Berg M. Mottram J.C. α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB. ChemMedChem 2010 5 10 1734 1748 10.1002/cmdc.201000265 20799311
    [Google Scholar]
  231. Saini S. Bharati K. Shaha C. Mukhopadhyay C.K. Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani. Sci. Rep. 2017 7 1 10488 10.1038/s41598‑017‑10041‑6 28874760
    [Google Scholar]
  232. Chakrabarti A. Narayana C. Joshi N. Metalloprotease Gp63-targeting novel glycoside exhibits potential antileishmanial activity. Front. Cell. Infect. Microbiol. 2022 12 803048 10.3389/fcimb.2022.803048 35601095
    [Google Scholar]
  233. Mao W. Daligaux P. Lazar N. Biochemical analysis of leishmanial and human GDP-Mannose Pyrophosphorylases and selection of inhibitors as new leads. Sci. Rep. 2017 7 1 751 765 10.1038/s41598‑017‑00848‑8 28389670
    [Google Scholar]
  234. Pomel S. Mao W. Ha-Duong T. Cavé C. Loiseau P.M. GDP-mannose pyrophosphorylase: A biologically validated target for drug development against leishmaniasis. Front. Cell. Infect. Microbiol. 2019 9 186 10.3389/fcimb.2019.00186 31214516
    [Google Scholar]
  235. Yasmeen S. Ansari W.A. Hassan F. Khan M.F. Drug repurposing against phosphomannomutase for the treatment of cutaneous Leishmaniasis. Orient. J. Chem. 2023 39 1 1 10 10.13005/ojc/390101
    [Google Scholar]
  236. Li H. Ji T. Sun Q. Chen Y. Xu W. Huang C. Structural insights into selective inhibition of leishmanial GDP-mannose pyrophosphorylase. Cell Discov. 2022 8 1 83 87 10.1038/s41421‑022‑00424‑z 36038534
    [Google Scholar]
  237. Pomel S. Rodrigo J. Hendra F. Cavé C. Loiseau P.M. In silico analysis of a therapeutic target in Leishmania infantum: The guanosine-diphospho-D-mannose pyrophosphorylase. Parasite 2012 19 1 63 70 10.1051/parasite/2012191063 22314241
    [Google Scholar]
  238. Lackovic K. Parisot J.P. Sleebs N. Inhibitors of Leishmania GDP-mannose pyrophosphorylase identified by high-throughput screening of small-molecule chemical library. Antimicrob. Agents Chemother. 2010 54 5 1712 1719 10.1128/AAC.01634‑09 20160053
    [Google Scholar]
  239. Wijnant GJ Dumetz F Dirkx L Tackling Drug Resistance and Other Causes of Treatment Failure in Leishmaniasis. Front Trop Dis 2022 3 837460-, 1-837460, 23. 10.3389/fitd.2022.837460
    [Google Scholar]
  240. Singh VK Tiwari R Rajneesh Advancing treatment for Leishmaniasis: From overcoming challenges to embracing therapeutic innovations. ACS Infect. Dis. 2025 11 1 47 68 10.1021/acsinfecdis.4c00693 39737830
    [Google Scholar]
  241. Santi AMM Murta SMF Impact of genetic diversity and genome plasticity of Leishmania spp. in treatment and the search for novel chemotherapeutic targets Front Cell Infect Microbiol 2022 12 826287-, 1-826287, 9. 10.3389/fcimb.2022.826287 35141175
    [Google Scholar]
  242. Lye L.F. Lin C.F. Ou Y.C. Chen C.M. Recent advances in antileishmanial drugs: New leishmaniasis medicine through repurposing approach. Tungs’. Med. J. 2024 18 Suppl. 1 S1 S5 10.4103/ETMJ.ETMJ‑D‑24‑00017
    [Google Scholar]
  243. Clinical trial synopsis 2020 https://dndi.org/wp-content/uploads/2023/10/DNDi-LXE408-01-VL-Clinical-Trial-Protocol-Synopsis.pdf
  244. Pal R Teli G Akhtar MJ Matada GSP Synthetic product-based approach toward potential antileishmanial drug development. Eur J Med Chem 2024 263 115927-, 1-115927, 31. 10.1016/j.ejmech.2023.115927 37976706
    [Google Scholar]
  245. Ghilardi Lago J.H. Passero L.F.D. Recent advances and future challenges in drug discovery for leishmaniasis based on natural products. Curr. Org. Chem. 2023 27 5 379 383 10.2174/1385272827666230430003735
    [Google Scholar]
  246. Majoor A. Michel G. Marty P. Boyer L. Pomares C. Leishmaniases: Strategies in treatment development. Parasite 2025 32 18 35 10.1051/parasite/2025009 40043198
    [Google Scholar]
  247. Nakweya G. Drug combination offers shorter, more effective visceral leishmaniasis treatment. Nature Africa 2022 Oct 10.1038/d44148‑022‑00138‑0
    [Google Scholar]
  248. Okwor I. Uzonna J. Social and economic burden of human leishmaniasis. Am. J. Trop. Med. Hyg. 2016 94 3 489 493 10.4269/ajtmh.15‑0408 26787156
    [Google Scholar]
  249. Karunaweera N.D. Ferreira M.U. Leishmaniasis: Current challenges and prospects for elimination with special focus on the South Asian region. Parasitology 2018 145 4 425 429 10.1017/S0031182018000471 29642962
    [Google Scholar]
  250. Singh R. Kashif M. Srivastava P. Manna P.P. Recent advances in chemotherapeutics for Leishmaniasis: Importance of the cellular biochemistry of the parasite and its molecular interaction with the host. Pathogens 2023 12 5 706 10.3390/pathogens12050706 37242374
    [Google Scholar]
  251. Ponte-Sucre A. Gamarro F. Dujardin J.C. Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Negl. Trop. Dis. 2017 11 12 0006052 10.1371/journal.pntd.0006052 29240765
    [Google Scholar]
  252. Bolz S.N. Schroeder M. Promiscuity in drug discovery on the verge of the structural revolution: Recent advances and future chances. Expert Opin. Drug Discov. 2023 18 9 973 985 10.1080/17460441.2023.2239700 37489516
    [Google Scholar]
  253. Maini R.N. Feldmann M. How does infliximab work in rheumatoid arthritis? Arthritis Res. 2002 4 Suppl. 2 S22 S28 10.1186/ar549 12110154
    [Google Scholar]
  254. Dalbeth N. Lauterio T.J. Wolfe H.R. Mechanism of action of colchicine in the treatment of gout. Clin. Ther. 2014 36 10 1465 1479 10.1016/j.clinthera.2014.07.017 25151572
    [Google Scholar]
  255. Tolou-Ghamari Z. Zare M. Habibabadi J.M. Najafi M.R. A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012. J. Res. Med. Sci. 2013 18 Suppl. 1 S81 S85 23961295
    [Google Scholar]
  256. Salerni B.L. Bates D.J. Albershardt T.C. Lowrey C.H. Eastman A. Vinblastine induces acute, cell cycle phase-independent apoptosis in some leukemias and lymphomas and can induce acute apoptosis in others when Mcl-1 is suppressed. Mol. Cancer Ther. 2010 9 4 791 802 10.1158/1535‑7163.MCT‑10‑0028 20371726
    [Google Scholar]
  257. Corona S.P. Generali D. Abemaciclib: A CDK4/6 inhibitor for the treatment of HR+/HER2– advanced breast cancer. Drug Des. Devel. Ther. 2018 12 321 330 10.2147/DDDT.S137783 29497278
    [Google Scholar]
  258. Kataria P. Surela N. Chaudhary A. Das J. Mirna: Biological regulator in host-parasite interaction during malaria infection. Int. J. Environ. Res. Public Health 2022 19 4 2395 10.3390/ijerph19042395 35206583
    [Google Scholar]
  259. Rashidi S. Mansouri R. Ali-Hassanzadeh M. Highlighting the interplay of micrornas from Leishmania parasites and infected-host cells. Parasitology 2021 148 12 1434 1446 10.1017/S0031182021001177 34218829
    [Google Scholar]
  260. Fernandes J.C.R. Muxel S.M. López-Gonzálvez M.A. Barbas C. Floeter-Winter L.M. Early Leishmania infectivity depends on miR-372/373/520d family-mediated reprogramming of polyamines metabolism in THP-1-derived macrophages. Sci. Rep. 2024 14 1 996 10.1038/s41598‑024‑51511‑y 38200138
    [Google Scholar]
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Biological Targets in Leishmaniasis and the Identification of the Next
Bentham Science Publishers ; https://doi.org/10.2174/0115748855407118251114095002
/content/journals/cdth/10.2174/0115748855407118251114095002
/content/journals/cdth/10.2174/0115748855407118251114095002
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  • Article Type:     Review Article
Keywords: chemotherapeutic ; multitarget inhibitors ; metabolic pathway ; multitarget ; pathogenesis ; Leishmaniasis

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