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2000
Volume 23, Issue 4
  • ISSN: 2211-3525
  • E-ISSN: 2211-3533

Abstract

Malaria is caused by protozoan parasites and is a significant contributor to global mortality and morbidity. The main reasons for the resurgence of malaria are the emergence of drug-resistant strains of the parasite and the ineffectiveness of current treatment. Pyrazole-based drugs play a crucial role in medicinal chemistry due to their diverse pharmacological properties. The pyrazole structure, a five-membered ring with two nitrogen atoms, is a key pharmacophore in various therapeutic agents. Numerous derivatives of pyrazole scaffold exhibited a wide range of pharmacological activity such as analgesics, antiinflammatory, antioxidant, antimicrobial, antidiabetic, anticancer, antiviral, antifungal, and antithrombotic activities. These drugs provide numerous opportunities for enhancing antimalarial agents by targeting various critical receptors. Various pyrazole derivatives have been reported to inhibit enzymes, receptors, and other targets to manage malaria. These derivatives inhibited parasite through various mechanisms such as falcipain, dihydrofolate redcutase, dihydroorotate dehydrogenase, lactate dehydrogenase, protein kinase, calcium dependent protein kinase, glycogen synthase kinase, and histo aspartic protease. Currently, researchers are developing new pyrazole-based derivatives, often in combination with other moieties, for improved malaria treatment. This review highlights the recent therapeutic advancements of pyrazole, including its structure-activity relationship, molecular docking, commercial drug availability, and a summary of recent research publications, all of which collectively assist scientists in developing effective drugs with desired pharmacological activities.

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References

  1. CuiL. MharakurwaS. NdiayeD. RathodP.K. RosenthalP.J. Antimalarial drug resistance: literature review and activities and findings of the ICEMR network.Am. J. Trop. Med. Hyg.2015933Suppl.576810.4269/ajtmh.15‑0007 26259943
    [Google Scholar]
  2. Ntie-KangF. OnguénéP.A. LifongoL.L. NdomJ.C. SipplW. MbazeL.M. The potential of anti-malarial compounds derived from African medicinal plants, part II: a pharmacological evaluation of non-alkaloids and non-terpenoids.Malar. J.20141318110.1186/1475‑2875‑13‑81 24602358
    [Google Scholar]
  3. MungaiM. TegtmeierG. ChamberlandM. PariseM. Transfusion-transmitted malaria in the united states from 1963 through 1999.N. Engl. J. Med.2001344261973197810.1056/NEJM200106283442603 11430326
    [Google Scholar]
  4. NiederhauserC. GalelS.A. Transfusion-transmitted malaria and mitigation strategies in nonendemic regions.Transfus. Med. Hemother.202249420521710.1159/000525414
    [Google Scholar]
  5. VermaA. JoshiH. SinghV. AnvikarA. ValechaN. Plasmodium vivax msp-3α polymorphisms: analysis in the Indian subcontinent.Malar. J.201615149210.1186/s12936‑016‑1524‑y 27663527
    [Google Scholar]
  6. JoshiH. PrajapatiS.K. VermaA. Kang’aS. CarltonJ.M. Plasmodium vivax in India.Trends Parasitol.200824522823510.1016/j.pt.2008.01.007 18403267
    [Google Scholar]
  7. González-CerónL. Martinez-BarnetcheJ. Montero-SolísC. SantillánF. SotoA.M. RodríguezM.H. EspinosaB.J. ChávezO.A. Molecular epidemiology of Plasmodium vivax in Latin America: polymorphism and evolutionary relationships of the circumsporozoite gene.Malar. J.201312124310.1186/1475‑2875‑12‑243 23855807
    [Google Scholar]
  8. World Malaria Report 2021.Geneva: World Health Organization2021
    [Google Scholar]
  9. RansonH. LissendenN. Insecticide resistance in African Anopheles mosquitoes: A worsening situation that needs urgent action to maintain malaria control.Trends Parasitol.201632318719610.1016/j.pt.2015.11.010 26826784
    [Google Scholar]
  10. WhiteN.J. Antimalarial drug resistance.J. Clin. Invest.200411381084109210.1172/JCI21682 15085184
    [Google Scholar]
  11. BlascoB. LeroyD. FidockD.A. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic.Nat. Med.201723891792810.1038/nm.4381 28777791
    [Google Scholar]
  12. ShiffC. Integrated approach to malaria control.Clin. Microbiol. Rev.200215227829310.1128/CMR.15.2.278‑293.2002 11932233
    [Google Scholar]
  13. PatesH. CurtisC. Mosquito behavior and vector control.Annu. Rev. Entomol.2005501537010.1146/annurev.ento.50.071803.130439 15355233
    [Google Scholar]
  14. malERA Consultative Group on Vector Control. A research agenda for malaria eradication: vector control.PLoS Med.201181e100040110.1371/journal.pmed.1000401 21311587
    [Google Scholar]
  15. OjurongbeO. AkindeleA.A. AdedokunS.A. ThomasB.N. Malaria: control, elimination, and eradication.Hum. Parasit. Dis. (Auckl.)20168111510.4137/HPD.S16590
    [Google Scholar]
  16. RoutS. MahapatraR.K. Plasmodium falciparum: Multidrug resistance.Chem. Biol. Drug Des.201993573775910.1111/cbdd.13484 30663249
    [Google Scholar]
  17. MitaT. TanabeK. KitaK. Spread and evolution of Plasmodium falciparum drug resistance.Parasitol. Int.200958320120910.1016/j.parint.2009.04.004 19393762
    [Google Scholar]
  18. TravassosM.A. LauferM.K. Resistance to antimalarial drugs: molecular, pharmacologic, and clinical considerations.Pediatr. Res.2009655 Part 264R70R10.1203/PDR.0b013e3181a0977e 19918214
    [Google Scholar]
  19. KumarS. BhardwajT.R. PrasadD.N. SinghR.K. Drug targets for resistant malaria: Historic to future perspectives.Biomed. Pharmacother.201810482710.1016/j.biopha.2018.05.009 29758416
    [Google Scholar]
  20. HydeJ.E. Drug‐resistant malaria − an insight.FEBS J.2007274184688469810.1111/j.1742‑4658.2007.05999.x 17824955
    [Google Scholar]
  21. Guidelines for the Treatment of Malaria.World Health Organization2015
    [Google Scholar]
  22. van der PluijmR.W. ImwongM. ChauN.H. HoaN.T. Thuy-NhienN.T. ThanhN.V. JittamalaP. HanboonkunupakarnB. ChutasmitK. SaelowC. RunjarernR. KaewmokW. TripuraR. PetoT.J. YokS. SuonS. SrengS. MaoS. OunS. YenS. AmaratungaC. LekD. HuyR. DhordaM. ChotivanichK. AshleyE.A. MukakaM. WaithiraN. CheahP.Y. MaudeR.J. AmatoR. PearsonR.D. GonçalvesS. JacobC.G. HamiltonW.L. FairhurstR.M. TarningJ. WinterbergM. KwiatkowskiD.P. PukrittayakameeS. HienT.T. DayN.P.J. MiottoO. WhiteN.J. DondorpA.M. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study.Lancet Infect. Dis.201919995296110.1016/S1473‑3099(19)30391‑3 31345710
    [Google Scholar]
  23. Whegang YoudomS. ChiabiA. BascoL.K. Monitoring the efficacy and safety of artemisinin-based combination therapies: a review and network meta-analysis of antimalarial therapeutic efficacy trials in Cameroon.Drugs R D.201919111410.1007/s40268‑018‑0259‑3 30656608
    [Google Scholar]
  24. ArieyF. WitkowskiB. AmaratungaC. BeghainJ. LangloisA.C. KhimN. KimS. DuruV. BouchierC. MaL. LimP. LeangR. DuongS. SrengS. SuonS. ChuorC.M. BoutD.M. MénardS. RogersW.O. GentonB. FandeurT. MiottoO. RingwaldP. Le BrasJ. BerryA. BaraleJ.C. FairhurstR.M. Benoit-VicalF. Mercereau-PuijalonO. MénardD. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.Nature20145057481505510.1038/nature12876 24352242
    [Google Scholar]
  25. WitkowskiB. AmaratungaC. KhimN. SrengS. ChimP. KimS. LimP. MaoS. SophaC. SamB. AndersonJ.M. DuongS. ChuorC.M. TaylorW.R.J. SuonS. Mercereau-PuijalonO. FairhurstR.M. MenardD. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies.Lancet Infect. Dis.201313121043104910.1016/S1473‑3099(13)70252‑4 24035558
    [Google Scholar]
  26. StraimerJ. GnädigN.F. WitkowskiB. AmaratungaC. DuruV. RamadaniA.P. DacheuxM. KhimN. ZhangL. LamS. GregoryP.D. UrnovF.D. Mercereau-PuijalonO. Benoit-VicalF. FairhurstR.M. MénardD. FidockD.A. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates.Science2015347622042843110.1126/science.1260867 25502314
    [Google Scholar]
  27. DasS. SahaB. HatiA.K. RoyS. Evidence of artemisinin-resistant Plasmodium falciparum malaria in eastern India.N. Engl. J. Med.2018379201962196410.1056/NEJMc1713777 30428283
    [Google Scholar]
  28. van der PluijmR.W. AmaratungaC. DhordaM. DondorpA.M. Triple artemisinin-based combination therapies for malaria–a new paradigm?Trends Parasitol.2021371152410.1016/j.pt.2020.09.011 33060063
    [Google Scholar]
  29. Faheem DeyS. JohriS. AbiramiM. Kumar, B.K.; Taramelli, D.; Basilico, N.; Balana-Fouce, R.; Gowri Chandra Sekhar, K.V.; Murugesan, S. Search for structurally diverse heterocyclic analogs as dual-acting antimalarial and antileishmanial agents: An overview.European J. Med. Chem. Rep.2022410003110.1016/j.ejmcr.2022.100031
    [Google Scholar]
  30. QinH.L. ZhangZ.W. LekkalaR. AlsulamiH. RakeshK.P. Chalcone hybrids as privileged scaffolds in antimalarial drug discovery: A key review.Eur. J. Med. Chem.202019311221510.1016/j.ejmech.2020.112215 32179331
    [Google Scholar]
  31. YangJ. WangY. GuanW. SuW. LiG. ZhangS. YaoH. Spiral molecules with antimalarial activities: A review.Eur. J. Med. Chem.202223711436110.1016/j.ejmech.2022.114361 35461019
    [Google Scholar]
  32. PatelO.P.S. BeteckR.M. LegoabeL.J. Antimalarial application of quinones: A recent update.Eur. J. Med. Chem.202121011308410.1016/j.ejmech.2020.113084 33333397
    [Google Scholar]
  33. KüçükgüzelŞ.G. ŞenkardeşS. Recent advances in bioactive pyrazoles.Eur. J. Med. Chem.2015979778681510.1016/j.ejmech.2014.11.059 25555743
    [Google Scholar]
  34. KumarV. KaurK. GuptaG.K. SharmaA.K. Pyrazole containing natural products: Synthetic preview and biological significance.Eur. J. Med. Chem.20136973575310.1016/j.ejmech.2013.08.053 24099993
    [Google Scholar]
  35. VermaR. VermaS.K. RakeshK.P. GirishY.R. AshrafizadehM. Sharath KumarK.S. RangappaK.S. Pyrazole-based analogs as potential antibacterial agents against methicillin-resistance staphylococcus aureus (MRSA) and its SAR elucidation.Eur. J. Med. Chem.202121211313410.1016/j.ejmech.2020.113134 33395624
    [Google Scholar]
  36. BennaniF.E. DoudachL. CherrahY. RamliY. KarrouchiK. AnsarM. FaouziM.E.A. Overview of recent developments of pyrazole derivatives as an anticancer agent in different cell line.Bioorg. Chem.20209710347010.1016/j.bioorg.2019.103470 32120072
    [Google Scholar]
  37. OubellaA. BimoussaA. ByadiS. FawziM. LaamariY. AuhmaniA. MorjaniH. RobertA. RiahiA. Ait IttoM.Y. Design, synthesis, in vitro anticancer activity, and molecular docking studies of new (R)-carvone-pyrazole-1,2,3-triazoles.J. Mol. Struct.2022126513338310.1016/j.molstruc.2022.133383
    [Google Scholar]
  38. CherukumalliP.K.R. TadiboinaB.R. GulipalliK.C. BodigeS. BadavathV.N. SridharG. GangarapuK. Design and synthesis of novel urea derivatives of pyrimidine-pyrazoles as anticancer agents.J. Mol. Struct.2022125113193710.1016/j.molstruc.2021.131937
    [Google Scholar]
  39. ShingareR. PatilY. SangshettiJ. PatilR. RajaniD. MadjeB. Docking simulations and primary assessment of newly synthesized benzene sulfonamide pyrazole oxadiazole derivatives as potential antimicrobial and antitubercular agents.Polycycl. Aromat. Compd.20234321799181110.1080/10406638.2022.2036771
    [Google Scholar]
  40. NidharM. KhanamS. SonkerP. GuptaP. MahapatraA. PatilS. YadavB.K. SinghR.K. Kumar TewariA. Click inspired novel pyrazole-triazole-persulfonimide & pyrazole-triazole-aryl derivatives; Design, synthesis, DPP-4 inhibitor with potential anti-diabetic agents.Bioorg. Chem.202212010558610.1016/j.bioorg.2021.105586 35051706
    [Google Scholar]
  41. ParikhP.H. TimaniyaJ.B. PatelM.J. PatelK.P. Microwave-assisted synthesis of pyrano[2,3-c]-pyrazole derivatives and their anti-microbial, anti-malarial, anti-tubercular, and anti-cancer activities.J. Mol. Struct.2022124913160510.1016/j.molstruc.2021.131605
    [Google Scholar]
  42. PayneM. BottomleyA.L. OchA. AsmaraA.P. HarryE.J. UngA.T. Synthesis and biological evaluation of 3,5-substituted pyrazoles as possible antibacterial agents.Bioorg. Med. Chem.20214811640110.1016/j.bmc.2021.116401 34555556
    [Google Scholar]
  43. AkolkarH.N. DengaleS.G. DeshmukhK.K. KaraleB.K. DarekarN.R. KhedkarV.M. ShaikhM.H. Design, synthesis and biological evaluation of novel furan & thiophene containing pyrazolyl pyrazolines as antimalarial agents.Polycycl. Aromat. Compd.20224251959197110.1080/10406638.2020.1821231
    [Google Scholar]
  44. KumarA. JainS. ChauhanS. AggarwalS. SainiD. Novel hybrids of quinoline with pyrazolylchalcones as potential antimalarial agents: Synthesis, biological evaluation, molecular docking and ADME prediction.Chem. Biol. Interact.202337311037910.1016/j.cbi.2023.110379 36738914
    [Google Scholar]
  45. GaoM. QuK. ZhangW. WangX. Pharmacological activity of pyrazole derivatives as an anticonvulsant for benefit against epilepsy.Neuroimmunomodulation2021282909810.1159/000513297 33774633
    [Google Scholar]
  46. BekhitA.A. NasrallaS.N. El-AgroudyE.J. HamoudaN. El-FattahA.A. BekhitS.A. AmagaseK. IbrahimT.M. Investigation of the anti-inflammatory and analgesic activities of promising pyrazole derivative.Eur. J. Pharm. Sci.202216810608010.1016/j.ejps.2021.106080 34818572
    [Google Scholar]
  47. R, K.; Bodke, Y.D. Synthesis, analgesic and anti-inflammatory activity of benzofuran pyrazole heterocycles.Chem. Data Collec.20202810045310.1016/j.cdc.2020.100453
    [Google Scholar]
  48. MarinescuM. Synthesis of antimicrobial benzimidazole–pyrazole compounds and their biological activities.Antibiotics (Basel)2021108100210.3390/antibiotics10081002 34439052
    [Google Scholar]
  49. WangX. WangA. QiuL. ChenM. LuA. LiG. YangC. XueW. Expedient discovery for novel antifungal leads targeting succinate dehydrogenase: pyrazole-4-formylhydrazide derivatives bearing a diphenyl ether fragment.J. Agric. Food Chem.202068491442614437
    [Google Scholar]
  50. LeT.G. KunduA. GhoshalA. Novel 1-methyl-1 h-pyrazole-5-carboxamide derivatives with potent anthelmintic activity.J. Med. Chem.201962733673380 30875218
    [Google Scholar]
  51. AbdellatifK.R.A. AbdelallE.K.A. ElshemyH.A.H. PhiloppesJ.N. HassaneinE.H.M. KahkN.M. Optimization of pyrazole-based compounds with 1,2,4-triazole-3-thiol moiety as selective COX-2 inhibitors cardioprotective drug candidates: Design, synthesis, cyclooxygenase inhibition, anti-inflammatory, ulcerogenicity, cardiovascular evaluation, and molecular modeling studies.Bioorg. Chem.202111410512210.1016/j.bioorg.2021.105122 34243075
    [Google Scholar]
  52. HassanG.S. Abou-SeriS.M. KamelG. AliM.M. Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents.Eur. J. Med. Chem.20147648249310.1016/j.ejmech.2014.02.033 24607877
    [Google Scholar]
  53. FriedrichG. RoseT. RisslerK. Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line sample preparation liquid chromatography with fluorescence detection.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.2002766229530510.1016/S0378‑4347(01)00514‑X 11824818
    [Google Scholar]
  54. SunH.Y. JiF.Q. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK.Biochem. Biophys. Res. Commun.2012423231932410.1016/j.bbrc.2012.05.120 22659414
    [Google Scholar]
  55. GutowskiG.E. SweeneyM.J. DeLongD.C. HamillR.L. GerzonK. DykeR.W. Biochemistry and biological effects of the pyrazofurins (pyrazomycins): initial clinical trial.Ann. N. Y. Acad. Sci.1975255154455110.1111/j.1749‑6632.1975.tb29257.x 1059372
    [Google Scholar]
  56. RolanP. HutchinsonM.R. JohnsonK.W. Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease.Expert Opin. Pharmacother.200910172897290410.1517/14656560903426189 19929708
    [Google Scholar]
  57. BaizmanE.R. EzrinA.M. FerrariR.A. LuttingerD. Pharmacologic profile of fezolamine fumarate: a nontricyclic antidepressant in animal models.J. Pharmacol. Exp. Ther.198724314054 3668867
    [Google Scholar]
  58. KameyamaT. NabeshimaT. YoshidaN. YamaguchiK. Neurochemical studies of an analgesic, 1,3-diphenyl-5-(2-dimethylaminopropionamide)-pyrazole [difenamizole].Res. Commun. Chem. Pathol. Pharmacol.19813113153 6454942
    [Google Scholar]
  59. ShoreN.D. Darolutamide (ODM-201) for the treatment of prostate cancer.Expert Opin. Pharmacother.201718994595210.1080/14656566.2017.1329820 28490267
    [Google Scholar]
  60. ChenY. TortoriciM.A. GarrettM. HeeB. KlamerusK.J. PithavalaY.K. Clinical pharmacology of axitinib.Clin. Pharmacokinet.201352971372510.1007/s40262‑013‑0068‑3 23677771
    [Google Scholar]
  61. KingreenJ.C. BregerG. [Pellagra in morazone abuse].Z. Hautkr.1984599573577 6145264
    [Google Scholar]
  62. TraceyW.R. AllenM.C. FrazierD.E. FossaA.A. JohnsonC.G. MaralaR.B. KnightD.R. Guzman-PerezA. Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1).Cardiovasc. Drug Rev.2003211173210.1111/j.1527‑3466.2003.tb00103.x 12595915
    [Google Scholar]
  63. TanakaH. NakagawaM. TakeuchiK. OkabeS. Effects of mepirizole and basic antiinflammatory drugs on HCl-ethanolinduced gastric lesions in rats.Dig. Dis. Sci.198934223824510.1007/BF01536058 2914545
    [Google Scholar]
  64. DrilonA. LaetschT.W. KummarS. DuBoisS.G. LassenU.N. DemetriG.D. NathensonM. DoebeleR.C. FaragoA.F. PappoA.S. TurpinB. DowlatiA. BroseM.S. MascarenhasL. FedermanN. BerlinJ. El-DeiryW.S. BaikC. DeekenJ. BoniV. NagasubramanianR. TaylorM. RudzinskiE.R. Meric-BernstamF. SohalD.P.S. MaP.C. RaezL.E. HechtmanJ.F. BenayedR. LadanyiM. TuchB.B. EbataK. CruickshankS. KuN.C. CoxM.C. HawkinsD.S. HongD.S. HymanD.M. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children.N. Engl. J. Med.2018378873173910.1056/NEJMoa1714448 29466156
    [Google Scholar]
  65. RohrbachK. ThomasM.A. GlickS. FungE.N. WangV. WatsonL. GregoryP. AntelJ. PelleymounterM.A. Ibipinabant attenuates β ‐cell loss in male Zucker diabetic fatty rats independently of its effects on body weight.Diabetes Obes. Metab.201214655556410.1111/j.1463‑1326.2012.01563.x 22268426
    [Google Scholar]
  66. MusshoffF. KraemerT. Identification of famprofazone ingestion.Int. J. Legal Med.1998111630530810.1007/s004140050176 9826089
    [Google Scholar]
  67. ArellanoF. SacristánJ.A. Metamizole: reassessment of its therapeutic role.Eur. J. Clin. Pharmacol.199038661761910.1007/BF00278592 2197099
    [Google Scholar]
  68. RothsteinJ.D. Edaravone: A new drug approved for ALS.Cell2017171472510.1016/j.cell.2017.10.011 29100067
    [Google Scholar]
  69. BrodieB.B. AxelrodJ. SobermanR. LevyB.B. The estimation of antipyrine in biological materials.J. Biol. Chem.19491791252910.1016/S0021‑9258(18)56807‑1 18119216
    [Google Scholar]
  70. FrancisS.E. SullivanD.J.Jr GoldbergD.E. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum.Annu. Rev. Microbiol.19975119712310.1146/annurev.micro.51.1.97 9343345
    [Google Scholar]
  71. LewV.L. TiffertT. GinsburgH. Excess hemoglobin digestion and the osmotic stability ofPlasmodium falciparum–infected red blood cells.Blood2003101104189419410.1182/blood‑2002‑08‑2654 12531811
    [Google Scholar]
  72. RosenthalP. SijwaliP. SinghA. ShenaiB. Cysteine proteases of malaria parasites: targets for chemotherapy.Curr. Pharm. Des.20028181659167210.2174/1381612023394197 12132997
    [Google Scholar]
  73. RosenthalP.J. Cysteine proteases of malaria parasites.Int. J. Parasitol.20043413-141489149910.1016/j.ijpara.2004.10.003 15582526
    [Google Scholar]
  74. SijwaliP.S. ShenaiB.R. GutJ. SinghA. RosenthalP.J. Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3.Biochem. J.2001360248148910.1042/bj3600481 11716777
    [Google Scholar]
  75. SijwaliP.S. RosenthalP.J. Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum.Proc. Natl. Acad. Sci. USA2004101134384438910.1073/pnas.0307720101 15070727
    [Google Scholar]
  76. SijwaliP.S. KooJ. SinghN. RosenthalP.J. Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum.Mol. Biochem. Parasitol.200615019610610.1016/j.molbiopara.2006.06.013 16890302
    [Google Scholar]
  77. RosenthalP.J. WollishW.S. PalmerJ.T. RasnickD. Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase.J. Clin. Invest.19918851467147210.1172/JCI115456 1939639
    [Google Scholar]
  78. SinghA. RosenthalP.J. Comparison of efficacies of cysteine protease inhibitors against five strains of Plasmodium falciparum.Antimicrob. Agents Chemother.200145394995110.1128/AAC.45.3.949‑951.2001 11181388
    [Google Scholar]
  79. ShenaiB.R. LeeB.J. Alvarez-HernandezA. ChongP.Y. EmalC.D. NeitzR.J. RoushW.R. RosenthalP.J. Structure-activity relationships for inhibition of cysteine protease activity and development of Plasmodium falciparum by peptidyl vinyl sulfones.Antimicrob. Agents Chemother.200347115416010.1128/AAC.47.1.154‑160.2003 12499184
    [Google Scholar]
  80. EttariR. BovaF. ZappalàM. GrassoS. MicaleN. Falcipain‐2 inhibitors.Med. Res. Rev.201030113616710.1002/med.20163 19526594
    [Google Scholar]
  81. SajidM. McKerrowJ.H. Cysteine proteases of parasitic organisms.Mol. Biochem. Parasitol.2002120112110.1016/S0166‑6851(01)00438‑8 11849701
    [Google Scholar]
  82. SchirmeisterT. KaepplerU. Non-peptidic inhibitors of cysteine proteases.Mini Rev. Med. Chem.20033436137310.2174/1389557033488079 12678829
    [Google Scholar]
  83. MelnykP. LerouxV. SergheraertC. GrellierP. Design, synthesis and in vitro antimalarial activity of an acylhydrazone library.Bioorg. Med. Chem. Lett.2006161313510.1016/j.bmcl.2005.09.058 16263280
    [Google Scholar]
  84. IbezimA. OfokansiM.N. NdukweX. ChiamaC.S. ObiB.C. IsioguguO.N. IkechukwuP.E. OnwukaA.M. IhimS.A. AsegbeloyinJ.N. NwodoN.J. Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives.Malar. J.202221124310.1186/s12936‑022‑04266‑8 35996135
    [Google Scholar]
  85. GopinathanA. MoiduM. MukundanM. Ellickal NarayananS. NarayananH. AdhikariN. Design, synthesis and biological evaluation of several aromatic substituted chalcones as antimalarial agents.Drug Dev. Res.20208181048105610.1002/ddr.21727 32767369
    [Google Scholar]
  86. AggarwalS. PaliwalD. KaushikD. GuptaG.K. KumarA. Synthesis, antimalarial evaluation and SAR study of some 1, 3, 5-trisubstituted pyrazoline derivatives.Lett. Org. Chem.2019161080781710.2174/1570178616666190212145754
    [Google Scholar]
  87. VermaG. KhanM.F. Mohan NainwalL. IshaqM. AkhterM. BakhtA. AnwerT. AfrinF. IslamuddinM. HusainI. AlamM.M. ShaquiquzzamanM. Targeting malaria and leishmaniasis: Synthesis and pharmacological evaluation of novel pyrazole-1,3,4-oxadiazole hybrids. Part II.Bioorg. Chem.20198910298610.1016/j.bioorg.2019.102986 31146198
    [Google Scholar]
  88. VermaG. ChashooG. AliA. KhanM.F. AkhtarW. AliI. AkhtarM. AlamM.M. ShaquiquzzamanM. Synthesis of pyrazole acrylic acid based oxadiazole and amide derivatives as antimalarial and anticancer agents.Bioorg. Chem.20187710612410.1016/j.bioorg.2018.01.007 29353728
    [Google Scholar]
  89. Himangini; Pathak, D.P.; Sharma, V.; Kumar, S. Designing novel inhibitors against falcipain-2 of Plasmodium falciparum.Bioorg. Med. Chem. Lett.20182891566156910.1016/j.bmcl.2018.03.058 29602682
    [Google Scholar]
  90. AggarwalS. PaliwalD. KaushikD. GuptaG.K. KumarA. Pyrazole Schiff base hybrids as anti-malarial agents: synthesis, in vitro screening and computational study.Comb. Chem. High Throughput Screen.201821319420310.2174/1386207321666180213092911 29436997
    [Google Scholar]
  91. KumarP. KadyanK. DuhanM. SindhuJ. SinghV. SaharanB.S. Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents.Chem. Cent. J.201711111510.1186/s13065‑017‑0344‑7 29138944
    [Google Scholar]
  92. MarellaA. AkhterM. ShaquiquzzamanM. TanwarO. VermaG. AlamM.M. Synthesis, 3D-QSAR and docking studies of pyrimidine nitrile-pyrazoline: a novel class of hybrid antimalarial agents.Med. Chem. Res.20152431018103710.1007/s00044‑014‑1188‑5
    [Google Scholar]
  93. AgarwalA. SrivastavaK. PuriS.K. ChauhanP.M.S. Synthesis of substituted indole derivatives as a new class of antimalarial agents.Bioorg. Med. Chem. Lett.200515123133313610.1016/j.bmcl.2005.04.011 15925306
    [Google Scholar]
  94. SardarianA. DouglasK.T. ReadM. SimsP.F.G. HydeJ.E. ChitnumsubP. SirawarapornR. SirawarapornW. Pyrimethamine analogs as strong inhibitors of double and quadruple mutants of dihydrofolate reductase in human malaria parasites.Org. Biomol. Chem.20031696096410.1039/b211636g 12929634
    [Google Scholar]
  95. OlliaroP.L. YuthavongY. An overview of chemotherapeutic targets for antimalarial drug discovery.Pharmacol. Ther.19998129111010.1016/S0163‑7258(98)00036‑9 10190581
    [Google Scholar]
  96. ButcherG.A. SindenR.E. CurtisC. Malaria: New Ideas, Old Problems, New Technologies.Parasitology Today2000162434410.1016/S0169‑4758(99)01577‑X
    [Google Scholar]
  97. MurrayM.C. PerkinsM.E. Chemotherapy of malaria.Annual reports in Medicinal Chemistry199631141150
    [Google Scholar]
  98. EnserinkM. Malaria researchers wait for industry to join fight.Science200028754601956195810.1126/science.287.5460.1956 10755950
    [Google Scholar]
  99. MüllerI.B. HydeJ.E. Folate metabolism in human malaria parasites—75 years on.Mol. Biochem. Parasitol.20131881637710.1016/j.molbiopara.2013.02.008 23500968
    [Google Scholar]
  100. Pyrimethamine & Sulfadoxine. United States National Library of Medicine.Available from: http://livertox.nih.gov/PyrimethamineSulfadoxine.htm
  101. Pyrimethamine and Sulfadoxine (Oral Route)Mayo Clinic. Mayo Foundation for Medical Educatin and Research.2011Available from: http://www.mayoclinic.com/health/drug-information/DR600357
    [Google Scholar]
  102. PornthanakasemW. RiangrungrojP. ChitnumsubP. IttaratW. KongkasuriyachaiD. UthaipibullC. YuthavongY. LeartsakulpanichU. Role of Plasmodium vivax dihydropteroate synthase polymorphisms in sulfa drug resistance.Antimicrob. Agents Chemother.20166084453446310.1128/AAC.01835‑15 27161627
    [Google Scholar]
  103. MokmakW. ChunsrivirotS. HannongbuaS. YuthavongY. TongsimaS. KamchonwongpaisanS. Molecular dynamics of interactions between rigid and flexible antifolates and dihydrofolate reductase from pyrimethamine-sensitive and pyrimethamine-resistant Plasmodium falciparum.Chem. Biol. Drug Des.201484445046110.1111/cbdd.12334 24716467
    [Google Scholar]
  104. BekhitA.A. NasrallaS.N. BekhitS.A. BekhitA.E. Novel dual acting antimalarial antileishmanial agents derived from pyrazole moiety.Biointerface Res. Appl. Chem.20221262256233
    [Google Scholar]
  105. GogoiP. ShakyaA. GhoshS.K. GogoiN. GahtoriP. SinghN. BhattacharyyaD.R. SinghU.P. BhatH.R. In silico study, synthesis, and evaluation of the antimalarial activity of hybrid dimethoxy pyrazole 1,3,5‐triazine derivatives.J. Biochem. Mol. Toxicol.2021353e2268210.1002/jbt.22682 33332673
    [Google Scholar]
  106. OthmanI.M.M. Gad-ElkareemM.A.M. AmrA.E.G.E. Al-OmarM.A. NossierE.S. ElsayedE.A. Novel heterocyclic hybrids of pyrazole targeting dihydrofolate reductase: design, biological evaluation and in silico studies.J. Enzyme Inhib. Med. Chem.20203511491150210.1080/14756366.2020.1791842 32668994
    [Google Scholar]
  107. VekariyaM.K. PatelD.B. PandyaP.A. VekariyaR.H. ShahP.U. RajaniD.P. ShahN.K. Novel N-thioamide analogues of pyrazolylpyrimidine based piperazine: Design, synthesis, characterization, in-silico molecular docking study and biological evaluation.J. Mol. Struct.2019117555156510.1016/j.molstruc.2018.08.018
    [Google Scholar]
  108. BekhitA.A. SaudiM.N. HassanA.M.M. FahmyS.M. IbrahimT.M. GhareebD. El-SeidyA.M. NasrallaS.N. BekhitA.E.D.A. Synthesis, in silico experiments and biological evaluation of 1,3,4-trisubstituted pyrazole derivatives as antimalarial agents.Eur. J. Med. Chem.201916335336610.1016/j.ejmech.2018.11.067 30530172
    [Google Scholar]
  109. LohidakshanK. RajanM. GaneshA. PaulM. JerinJ. Pass and Swiss ADME collaborated in silico docking approach to the synthesis of certain pyrazoline spacer compounds for dihydrofolate reductase inhibition and antimalarial activity.Bangladesh J. Pharmacol.2018131232910.3329/bjp.v13i1.33625
    [Google Scholar]
  110. SapariyaN.H. VaghasiyaB.K. ThummarR.P. KamaniR.D. PatelK.H. ThakorP. ThakkarS.S. RayA. RavalD.K. Synthesis, characterization, in silico molecular docking study and biological evaluation of a 5-(phenylthio) pyrazole based polyhydroquinoline core moiety.New J. Chem.20174119106861069410.1039/C7NJ01962A
    [Google Scholar]
  111. BhattJ.D. ChudasamaC.J. PatelK.D. Microwave assisted synthesis of pyrimidines in ionic liquid and their potency as non‐classical malarial antifolates.Arch. Pharm. (Weinheim)20163491079180010.1002/ardp.201600148 27528517
    [Google Scholar]
  112. BhattJ.D. ChudasamaC.J. PatelK.D. diarylpyrazole ligated dihydropyrimidine hybrids as potent non‐classical antifolates and their efficacy against Plasmodium falciparum.Arch. Pharm. (Weinheim)20173509170008810.1002/ardp.201700088 28796406
    [Google Scholar]
  113. BekhitA.A. HassanA.M.M. Abd El RazikH.A. El-MiligyM.M.M. El-AgroudyE.J. BekhitA.E.D.A. New heterocyclic hybrids of pyrazole and its bioisosteres: Design, synthesis and biological evaluation as dual acting antimalarial-antileishmanial agents.Eur. J. Med. Chem.201594304410.1016/j.ejmech.2015.02.038 25768697
    [Google Scholar]
  114. SinghA. MaqboolM. MobashirM. HodaN. Dihydroorotate dehydrogenase: A drug target for the development of antimalarials.Eur. J. Med. Chem.201712564065110.1016/j.ejmech.2016.09.085 27721149
    [Google Scholar]
  115. HoelzL.V.B. CalilF.A. NonatoM.C. PinheiroL.C.S. BoechatN. Plasmodium falciparum dihydroorotate dehydrogenase: a drug target against malaria.Future Med. Chem.201810151853187410.4155/fmc‑2017‑0250 30019917
    [Google Scholar]
  116. Phillips MA. Rathod PK. Plasmodium dihydroorotate dehydrogenase: A promising target for novel anti-malarial chemotherapy.Infectious Disorders-Drug Targets2010103226239
    [Google Scholar]
  117. GardnerM.J. HallN. FungE. WhiteO. BerrimanM. HymanR.W. CarltonJ.M. PainA. NelsonK.E. BowmanS. PaulsenI.T. JamesK. EisenJ.A. RutherfordK. SalzbergS.L. CraigA. KyesS. ChanM.S. NeneV. ShallomS.J. SuhB. PetersonJ. AngiuoliS. PerteaM. AllenJ. SelengutJ. HaftD. MatherM.W. VaidyaA.B. MartinD.M.A. FairlambA.H. FraunholzM.J. RoosD.S. RalphS.A. McFaddenG.I. CummingsL.M. SubramanianG.M. MungallC. VenterJ.C. CarucciD.J. HoffmanS.L. NewboldC. DavisR.W. FraserC.M. BarrellB. Genome sequence of the human malaria parasite Plasmodium falciparum.Nature2002419690649851110.1038/nature01097 12368864
    [Google Scholar]
  118. VahL. MedvedT. GrošeljU. KlemenčičM. PodlipnikČ. ŠtefaneB. WaggerJ. NovinecM. SveteJ. Regioselective Synthesis of 5- and 3-Hydroxy-N-Aryl-1H-Pyrazole-4-Carboxylates and Their Evaluation as Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase.Molecules20222715476410.3390/molecules27154764 35897941
    [Google Scholar]
  119. Haredi AbdelmonsefA. Eldeeb MohamedM. El-NaggarM. TemairkH. Mohamed MosallamA. Novel quinazolin-2, 4-dione hybrid molecules as possible inhibitors against malaria: synthesis and in silico molecular docking studies.Front. Mol. Biosci.2020710510.3389/fmolb.2020.00105 32582763
    [Google Scholar]
  120. PippioneA.C. SainasS. GoyalP. FritzsonI. CassianoG.C. GiraudoA. GiorgisM. TavellaT.A. BagnatiR. RolandoB. Caing-CarlssonR. CostaF.T.M. AndradeC.H. Al-KaradaghiS. BoschiD. FriemannR. LolliM.L. Hydroxyazole scaffold-based Plasmodium falciparum dihydroorotate dehydrogenase inhibitors: Synthesis, biological evaluation and X-ray structural studies.Eur. J. Med. Chem.201916326628010.1016/j.ejmech.2018.11.044 30529545
    [Google Scholar]
  121. StrašekN. LavrenčičL. OštrekA. SlapšakD. GrošeljU. KlemenčičM. Brodnik ŽugeljH. WaggerJ. NovinecM. SveteJ. Tetrahydro-1H,5H-pyrazolo[1,2-a]pyrazole-1-carboxylates as inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase.Bioorg. Chem.20198910298210.1016/j.bioorg.2019.102982 31132601
    [Google Scholar]
  122. AzeredoL.F.S.P. CoutinhoJ.P. JaborV.A.P. FelicianoP.R. NonatoM.C. KaiserC.R. MenezesC.M.S. HammesA.S.O. CaffarenaE.R. HoelzL.V.B. de SouzaN.B. PereiraG.A.N. CerávoloI.P. KrettliA.U. BoechatN. Evaluation of 7-arylaminopyrazolo[1,5-a]pyrimidines as anti-Plasmodium falciparum, antimalarial, and Pf-dihydroorotate dehydrogenase inhibitors.Eur. J. Med. Chem.2017126728310.1016/j.ejmech.2016.09.073 27744189
    [Google Scholar]
  123. KannanM. RaichurkarA.V. KhanF.R.N. IyerP.S. Synthesis and in vitro evaluation of novel 8-aminoquinoline–pyrazolopyrimidine hybrids as potent antimalarial agents.Bioorg. Med. Chem. Lett.20152551100110310.1016/j.bmcl.2015.01.003 25650255
    [Google Scholar]
  124. Lang-UnnaschN. MurphyA.D. Metabolic changes of the malaria parasite during the transition from the human to the mosquito host.Annu. Rev. Microbiol.199852156159010.1146/annurev.micro.52.1.561 9891808
    [Google Scholar]
  125. GomezM.S. PiperR.C. HunsakerL.A. RoyerR.E. DeckL.M. MaklerM.T. Vander JagtD.L. Substrate and cofactor specificity and selective inhibition of lactate dehydrogenase from the malarial parasite P. falciparum.Mol. Biochem. Parasitol.199790123524610.1016/S0166‑6851(97)00140‑0 9497046
    [Google Scholar]
  126. MentingJ.G.T. TilleyL. DeadyL.W. NgK. CowmanA.F. FoleyM. FoleyM. The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from Plasmodium falciparum.Mol. Biochem. Parasitol.1997881-221522410.1016/S0166‑6851(97)00095‑9 9274881
    [Google Scholar]
  127. ReadJ.A. WilkinsonK.W. TranterR. SessionsR.B. BradyR.L. Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate dehydrogenase.J. Biol. Chem.199927415102131021810.1074/jbc.274.15.10213 10187806
    [Google Scholar]
  128. ShamsuddinM.A. AliA.H. ZakariaN.H. MohammatM.F. HamzahA.S. ShaameriZ. LamK.W. Mark-LeeW.F. AgustarH.K. Mohd Abd RazakM.R. LatipJ. HassanN.I. Synthesis, molecular docking, and antimalarial activity of hybrid 4-aminoquinoline-pyrano [2, 3-c] pyrazole derivatives.Pharmaceuticals (Basel)20211411117410.3390/ph14111174 34832956
    [Google Scholar]
  129. ShamsuddinM.A. ZakariaN.H. MohammatM.F. SyahriJ. LatipJ. HassanN.I. Synthesis and Molecular Docking Studies of Pyrano [2, 3-c] Pyrazole-3-Carboxylates as Potential Inhibitors of Plasmodium falciparum.Malays. J. Chem.20202245261
    [Google Scholar]
  130. NasutionM. ArdiansahB. TambunanU.S. Chalcone and its pyrazole derivatives as potential Plasmodium falciparum lactate dehydrogenase inhibitor: In silico approach for new antimalarial drug.The 1st Asian Researcher Symposium2016
    [Google Scholar]
  131. Molecular modeling studies, synthesis and biological evaluation of novel Plasmodium falciparum lactate dehydrogenase (pfLDH) inhibitors.Antiinfect. Agents20121015571
    [Google Scholar]
  132. BoulocN. LargeJ.M. SmiljanicE. WhalleyD. AnsellK.H. EdlinC.D. BryansJ.S. Synthesis and in vitro evaluation of imidazopyridazines as novel inhibitors of the malarial kinase PfPK7.Bioorg. Med. Chem. Lett.200818195294529810.1016/j.bmcl.2008.08.043 18774709
    [Google Scholar]
  133. GeyerJ.A. KeenanS.M. WoodardC.L. ThompsonP.A. GerenaL. NicholsD.A. GutteridgeC.E. WatersN.C. Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenones.Bioorg. Med. Chem. Lett.20091971982198510.1016/j.bmcl.2009.02.042 19250824
    [Google Scholar]
  134. ChapmanT.M. OsborneS.A. WallaceC. BirchallK. BoulocN. JonesH.M. AnsellK.H. TaylorD.L. CloughB. GreenJ.L. HolderA.A. Optimization of an imidazopyridazine series of inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1).J. Med. Chem.20145783570358710.1021/jm500342d 24689770
    [Google Scholar]
  135. ChapmanT.M. OsborneS.A. BoulocN. LargeJ.M. WallaceC. BirchallK. AnsellK.H. JonesH.M. TaylorD. CloughB. GreenJ.L. HolderA.A. Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1).Bioorg. Med. Chem. Lett.201323103064306910.1016/j.bmcl.2013.03.017 23570789
    [Google Scholar]
  136. FugelW. OberholzerA.E. GschloesslB. DzikowskiR. PressburgerN. PreuL. PearlL.H. BaratteB. RatinM. OkunI. DoerigC. KruggelS. LemckeT. MeijerL. KunickC. 3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3- b]pyridine-5-carbonitriles Are Selective Inhibitors of Plasmodium falciparum Glycogen Synthase Kinase-3.J. Med. Chem.201356126427510.1021/jm301575n 23214499
    [Google Scholar]
  137. VidadalaR.S.R. OjoK.K. JohnsonS.M. ZhangZ. LeonardS.E. MitraA. ChoiR. ReidM.C. KeylounK.R. FoxA.M.W. KennedyM. Silver-BraceT. HumeJ.C.C. KappeS. VerlindeC.L.M.J. FanE. MerrittE.A. Van VoorhisW.C. MalyD.J. Development of potent and selective Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) inhibitors that block the transmission of malaria to mosquitoes.Eur. J. Med. Chem.20147456257310.1016/j.ejmech.2013.12.048 24531197
    [Google Scholar]
  138. HuangW. HulversonM.A. ZhangZ. ChoiR. HartK.J. KennedyM. VidadalaR.S.R. MalyD.J. Van VoorhisW.C. LindnerS.E. FanE. OjoK.K. 5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents.Bioorg. Med. Chem. Lett.201626225487549110.1016/j.bmcl.2016.10.014 27780638
    [Google Scholar]
  139. LargeJ.M. OsborneS.A. Smiljanic-HurleyE. AnsellK.H. JonesH.M. TaylorD.L. CloughB. GreenJ.L. HolderA.A. Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues.Bioorg. Med. Chem. Lett.201323216019602410.1016/j.bmcl.2013.08.010 24035097
    [Google Scholar]
  140. CoombsG.H. GoldbergD.E. KlembaM. BerryC. KayJ. MottramJ.C. Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets.Trends Parasitol.2001171153253710.1016/S1471‑4922(01)02037‑2 11872398
    [Google Scholar]
  141. KolakovichK.A. GluzmanI.Y. DuffinK.L. GoldbergD.E. Generation of hemoglobin peptides in the acidic digestive vacuole of Plasmodium falciparum implicates peptide transport in amino acid production.Mol. Biochem. Parasitol.199787212313510.1016/S0166‑6851(97)00062‑5 9247924
    [Google Scholar]
  142. BanerjeeR. LiuJ. BeattyW. PelosofL. KlembaM. GoldbergD.E. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine.Proc. Natl. Acad. Sci. USA200299299099510.1073/pnas.022630099 11782538
    [Google Scholar]
  143. ThillainayagamM. RamaiahS. AnbarasuA. Molecular docking and dynamics studies on novel benzene sulfonamide substituted pyrazole-pyrazoline analogues as potent inhibitors of Plasmodium falciparum Histo aspartic protease.J. Biomol. Struct. Dyn.202038113235324510.1080/07391102.2019.1654923 31411122
    [Google Scholar]
  144. YuM. KumarT.R.S. NkrumahL.J. CoppiA. RetzlaffS. LiC.D. KellyB.J. MouraP.A. LakshmananV. FreundlichJ.S. ValderramosJ.C. VilchezeC. SiednerM. TsaiJ.H.C. FalkardB. SidhuA.S. PurcellL.A. GratraudP. KremerL. WatersA.P. SchiehserG. JacobusD.P. JanseC.J. AgerA. JacobsW.R.Jr SacchettiniJ.C. HeusslerV. SinnisP. FidockD.A. The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.Cell Host Microbe20084656757810.1016/j.chom.2008.11.001 19064257
    [Google Scholar]
  145. HeathR.J. RockC.O. Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli.J. Biol. Chem.199527044265382654210.1074/jbc.270.44.26538 7592873
    [Google Scholar]
  146. QidwaiT. KhanF. Antimalarial drugs and drug targets specific to fatty acid metabolic pathway of Plasmodium falciparum.Chem. Biol. Drug Des.201280215517210.1111/j.1747‑0285.2012.01389.x 22487082
    [Google Scholar]
  147. HunteC. SolmazS. PalsdóttirH. WenzT. A structural perspective on mechanism and function of the cytochrome bc (1) complex.Results Probl. Cell Differ.20084525327810.1007/400_2007_042
    [Google Scholar]
  148. SrivastavaI.K. VaidyaA.B. A mechanism for the synergistic antimalarial action of atovaquone and proguanil.Antimicrob. Agents Chemother.19994361334133910.1128/AAC.43.6.1334 10348748
    [Google Scholar]
  149. EagonS. HammillJ.T. SigalM. AhnK.J. TryhornJ.E. KochG. BelangerB. ChaplanC.A. LoopL. KashtanovaA.S. YniguezK. LazaroH. WilkinsonS.P. RiceA.L. FaladeM.O. TakahashiR. KimK. CheungA. DiBernardoC. KimballJ.J. WinzelerE.A. EribezK. MittalN. GamoF.J. CrespoB. ChurchyardA. García-BarbazánI. BaumJ. AndersonM.O. LaleuB. GuyR.K. Synthesis and structure–activity relationship of dual-stage antimalarial pyrazolo [3, 4-b] pyridines.J. Med. Chem.20206320119021191910.1021/acs.jmedchem.0c01152 32945666
    [Google Scholar]
  150. SopitthummakhunK. ThongpanchangC. VilaivanT. YuthavongY. ChaiyenP. LeartsakulpanichU. Plasmodium serine hydroxymethyltransferase as a potential anti-malarial target: inhibition studies using improved methods for enzyme production and assay.Malar. J.201211119410.1186/1475‑2875‑11‑194 22691309
    [Google Scholar]
  151. MaenpuenS. SopitthummakhunK. YuthavongY. ChaiyenP. LeartsakulpanichU. Characterization of Plasmodium falciparum serine hydroxymethyltransferase-A potential antimalarial target.Mol. Biochem. Parasitol.20091681637310.1016/j.molbiopara.2009.06.010 19591881
    [Google Scholar]
  152. WitschelM.C. RottmannM. SchwabA. LeartsakulpanichU. ChitnumsubP. SeetM. TonazziS. SchwertzG. StelzerF. MietznerT. McNamaraC. ThaterF. FreymondC. JaruwatA. PinthongC. RiangrungrojP. OufirM. HamburgerM. MäserP. Sanz-AlonsoL.M. CharmanS. WittlinS. YuthavongY. ChaiyenP. DiederichF. Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities.J. Med. Chem.20155873117313010.1021/jm501987h 25785478
    [Google Scholar]
  153. PandyaK.M. PatelA.H. DesaiP.S. Development of antimicrobial, antimalarial and antitubercular compounds based on a quinoline-pyrazole clubbed scaffold derived via doebner reaction.Chemistry Africa202031899810.1007/s42250‑019‑00096‑5
    [Google Scholar]
  154. RaghuvanshiD.S. VermaN. SinghS.V. KhareS. PalA. NegiA.S. Synthesis of thymol-based pyrazolines: An effort to perceive novel potent-antimalarials.Bioorg. Chem.20198810293310.1016/j.bioorg.2019.102933 31048119
    [Google Scholar]
  155. BhattJ.D. PatelT.S. ChudasamaC.J. PatelK.D. Microwave‐Assisted Synthesis Of Novel Pyrazole Clubbed Polyhydroquinolines In An Ionic‐Liquid And Their Biological Perspective.ChemistrySelect20183133632364010.1002/slct.201702285
    [Google Scholar]
  156. KumarG. TanwarO. KumarJ. AkhterM. SharmaS. PillaiC.R. AlamM.M. ZamaM.S. Pyrazole-pyrazoline as promising novel antimalarial agents: A mechanistic study.Eur. J. Med. Chem.201814913914710.1016/j.ejmech.2018.01.082 29499486
    [Google Scholar]
  157. SilveiraF.F. FeitosaL.M. MafraJ.C.M. FerreiraM.L.G. RogerioK.R. CarvalhoL.J.M. BoechatN. PinheiroL.C.S. Synthesis and anti-Plasmodium falciparum evaluation of novel pyrazolopyrimidine derivatives.Med. Chem. Res.20182781876188410.1007/s00044‑018‑2199‑4
    [Google Scholar]
  158. PrasadP. KalolaA.G. PatelM.P. Microwave assisted one-pot synthetic route to imidazo[1,2- a]pyrimidine derivatives of imidazo/triazole clubbed pyrazole and their pharmacological screening.New J. Chem.20184215126661267610.1039/C8NJ00670A
    [Google Scholar]
  159. KamaniK.A. PatelK.D. Synthesis, characterization and biological evaluation of coumarin-pyrazole-pyrazoline hybrids.World J. Pharm. Res.20176939953
    [Google Scholar]
  160. Ramírez-PradaJ. RobledoS.M. VélezI.D. CrespoM.P. QuirogaJ. AboniaR. MontoyaA. SvetazL. ZacchinoS. InsuastyB. Synthesis of novel quinoline–based 4,5–dihydro–1 H –pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.Eur. J. Med. Chem.201713123725410.1016/j.ejmech.2017.03.016 28329730
    [Google Scholar]
  161. MishraV.K. MishraM. KashawV. KashawS.K. Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents.Bioorg. Med. Chem.20172561949196210.1016/j.bmc.2017.02.025 28237557
    [Google Scholar]
  162. PandeyA.K. SharmaS. PandeyM. AlamM.M. ShaquiquzzamanM. AkhterM. 4, 5-Dihydrooxazole-pyrazoline hybrids: Synthesis and their evaluation as potential antimalarial agents.Eur. J. Med. Chem.201612347648610.1016/j.ejmech.2016.07.055 27494165
    [Google Scholar]
  163. KaradS.C. PurohitV.B. ThakorP. ThakkarV.R. RavalD.K. Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities.Eur. J. Med. Chem.201611227027910.1016/j.ejmech.2016.02.016 26900659
    [Google Scholar]
  164. KaradS.C. PurohitV.B. AvalaniJ.R. SapariyaN.H. RavalD.K. Design, synthesis, and characterization of a fluoro substituted novel pyrazole nucleus clubbed with 1,3,4-oxadiazole scaffolds and their biological applications.RSC Advances2016647415324154110.1039/C6RA01349J
    [Google Scholar]
  165. InsuastyB. RamírezJ. BecerraD. EcheverryC. QuirogaJ. AboniaR. RobledoS.M. VélezI.D. UpeguiY. MuñozJ.A. OspinaV. NoguerasM. CoboJ. An efficient synthesis of new caffeine-based chalcones, pyrazolines and pyrazolo[3,4-b][1,4]diazepines as potential antimalarial, antitrypanosomal and antileishmanial agents.Eur. J. Med. Chem.20159340141310.1016/j.ejmech.2015.02.040 25725376
    [Google Scholar]
  166. MarellaA. ShaquiquzzamanM. AkhterM. VermaG. AlamM.M. Novel pyrazole–pyrazoline hybrids endowed with thioamide as antimalarial agents: their synthesis and 3D-QSAR studies.J. Enzyme Inhib. Med. Chem.201530459760610.3109/14756366.2014.958081 25333767
    [Google Scholar]
  167. KaradS.C. PurohitV.B. RavalD.K. KalariaP.N. AvalaniJ.R. ThakorP. ThakkarV.R. Green synthesis and pharmacological screening of polyhydroquinoline derivatives bearing a fluorinated 5-aryloxypyrazole nucleus.RSC Advances2015521160001600910.1039/C5RA00388A
    [Google Scholar]
  168. VaidyaA.B. MorriseyJ.M. ZhangZ. DasS. DalyT.M. OttoT.D. SpillmanN.J. WyvrattM. SieglP. MarfurtJ. WirjanataG. SebayangB.F. PriceR.N. ChatterjeeA. NagleA. StasiakM. CharmanS.A. Angulo-BarturenI. FerrerS. Belén Jiménez-DíazM. MartínezM.S. GamoF.J. AveryV.M. RueckerA. DelvesM. KirkK. BerrimanM. KortagereS. BurrowsJ. FanE. BergmanL.W. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum.Nat. Commun.201451552110.1038/ncomms6521 25422853
    [Google Scholar]
  169. SatasiaS.P. KalariaP.N. RavalD.K. Catalytic regioselective synthesis of pyrazole based pyrido[2,3-d]pyrimidine-diones and their biological evaluation.Org. Biomol. Chem.201412111751175810.1039/c3ob42132e 24496121
    [Google Scholar]
  170. KaradS.C. PurohitV.B. RavalD.K. Design, synthesis and characterization of fluoro substituted novel pyrazolylpyrazolines scaffold and their pharmacological screening.Eur. J. Med. Chem.201484515810.1016/j.ejmech.2014.07.008 25016227
    [Google Scholar]
  171. KalariaP.N. SatasiaS.P. RavalD.K. Synthesis, identification and in vitro biological evaluation of some novel 5-imidazopyrazole incorporated pyrazoline and isoxazoline derivatives.New J. Chem.20143872902291010.1039/c4nj00244j
    [Google Scholar]
  172. KalariaP.N. SatasiaS.P. RavalD.K. Synthesis, characterization and pharmacological screening of some novel 5-imidazopyrazole incorporated polyhydroquinoline derivatives.Eur. J. Med. Chem.20147820721610.1016/j.ejmech.2014.02.015 24681985
    [Google Scholar]
  173. KalariaP.N. SatasiaS.P. RavalD.K. Synthesis, characterization and biological screening of novel 5-imidazopyrazole incorporated fused pyran motifs under microwave irradiation.New J. Chem.20143841512152110.1039/c3nj01327h
    [Google Scholar]
  174. CheukaP.M. CabreraD.G. PaquetT. ChibaleK. Structure–activity relationship studies of antiplasmodial aminomethylthiazoles.Bioorg. Med. Chem. Lett.201424225207521110.1016/j.bmcl.2014.09.071 25316314
    [Google Scholar]
  175. InsuastyB. MontoyaA. BecerraD. QuirogaJ. AboniaR. RobledoS. VélezI.D. UpeguiY. NoguerasM. CoboJ. Synthesis of novel analogs of 2-pyrazoline obtained from [(7-chloroquinolin-4-yl)amino]chalcones and hydrazine as potential antitumor and antimalarial agents.Eur. J. Med. Chem.20136725226210.1016/j.ejmech.2013.06.049 23871905
    [Google Scholar]
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