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image of Hydrazones as Potential Antimelanoma Prototypes: A Systematic and Patent Review

Abstract

Introduction

Hydrazones are chemical compounds with the potential to inhibit various neoplasms, including melanoma, a highly metastatic and multidrug-resistant cancer. This study aimed to systematically review the literature and analyze patents to assess the potential of hydrazones as prototype anti-melanoma agents.

Methods

Following PRISMA guidelines (OSF registration: DOI 10.17605/OSF.IO/3AWR9), a systematic search was conducted in PubMed/Medline, Web of Science, ScienceDirect, and Scopus for studies published from January 2019 to February 2024 using the terms “hydrazone” and “melanoma”. Only original English-language studies with experimental evaluation of anti-melanoma activity, and/or , were included. Patent searches were also carried out in ESPACENET, WIPO, LENS, and Google Patents using the IPC code A61P35/00.

Results

From 1,072 records, 35 articles met eligibility criteria. All studies reported anti-melanoma activity of hydrazones; however, none included assays. N-acylhydrazones were the most frequently investigated subclass, featured in 19 studies. The patent analysis identified 41 filings using the combined terms “hydrazone AND melanoma”, with Google Patents accounting for the majority (29 filings).

Discussion

Hydrazones, particularly N-acylhydrazones, showed significant activity and selectivity, surpassing traditional drugs like cisplatin in some cases. The limited number of patent filings might indicate difficulties with protecting intellectual property, including effects from the COVID-19 pandemic. However, methodological differences and the lack of data are still major challenges. This emphasizes the need for more consistent and applicable research.

Conclusion

Despite their potential, further studies are needed to validate hydrazones as a distinct class of antineoplastic agents.

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2026-02-04
2026-02-28
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References

  1. Khan M. Alam F. Alam A. Wadood A. Shams S. Ali M. Shah S. AlAsmari A.F. Alharbi M. Alasmari F. Synthesis of some novel 4-bromobenzoic acid clubbed hydrazone schiff base derivatives as potent α-amylase inhibitors: In vitro and in silico studies. Lett. Drug Des. Discov. 2024 21 15 3186 3197 10.2174/0115701808262821231114114237
    [Google Scholar]
  2. Khattar T. Govindaiah P. Mishra A. Ansari M.D.M. Kaur P. A systematic review on hydrazones their chemistry and biological activities. AIP Conf Proc 2023 2804 020289 10.1063/5.0168993
    [Google Scholar]
  3. de Oliveira Carneiro Brum J. França T.C.C. LaPlante S.R. Villar J.D.F. Synthesis and biological activity of hydrazones and derivatives: A review. Mini Rev. Med. Chem. 2020 20 5 342 368 10.2174/1389557519666191014142448 31612828
    [Google Scholar]
  4. Maryam Z. Kaya B. Bostancı H.E. Kısa D. Çelik İ. Çevik U.A. Kaplancıklı Z.A. In vitro anti-Helicobacter pylori, anti-urease and anti-gastric cancer activities of novel hydrazones. J. Mol. Struct. 2024 1307 137961 10.1016/j.molstruc.2024.137961
    [Google Scholar]
  5. Shakoor A. Jan F. Rahman S. Ali M. Ibrahim M. Khan H. Alam A. Khan A. Ali A. Al-Olayan E. Abukhadra M.R. Al-Harrasi A. Khan M. Synthesis, urease inhibitory activity, molecular docking, dynamics, MMGBSA and DFT studies of hydrazone-Schiff bases bearing benzimidazole scaffold. Chem. Biodivers. 2025 22 3 202402096 10.1002/cbdv.202402096 39530214
    [Google Scholar]
  6. Alam F. Ismail M. Kamal M. Ur Rahman F. Alam A. AlAsmari A.F. Alasmari F. Khan M. Investigating the tyrosinase inhibitory activity of 4‐bromobenzoic acid hydrazone‐Schiff bases: In vitro, molecular structure and docking studies. ChemistrySelect 2024 9 44 202401987 10.1002/slct.202401987
    [Google Scholar]
  7. Medeiros M.A.M.B. Gama e Silva M. de Menezes Barbosa J. Martins de Lavor É. Ribeiro T.F. Macedo C.A.F. de Souza Duarte-Filho L.A.M. Feitosa T.A. de Jesus Silva J. Fokoue H.H. Araújo C.R.M. de Assis Gonsalves A. Augusto de Araújo Ribeiro L. Almeida J.R.G.S. Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice. PLoS One 2021 16 11 0258094 10.1371/journal.pone.0258094 34818331
    [Google Scholar]
  8. Cancer topics. 2024 Available from: https://www.iarc.who.int/cancer-topics/
  9. Guo W. Wang H. Li C. Signal pathways of melanoma and targeted therapy. Signal Transduct. Target. Ther. 2021 6 1 424 10.1038/s41392‑021‑00827‑6 34924562
    [Google Scholar]
  10. Schadendorf D. van Akkooi A.C.J. Berking C. Griewank K.G. Gutzmer R. Hauschild A. Stang A. Roesch A. Ugurel S. Melanoma. Lancet 2018 392 10151 971 984 10.1016/S0140‑6736(18)31559‑9 30238891
    [Google Scholar]
  11. Long G.V. Swetter S.M. Menzies A.M. Gershenwald J.E. Scolyer R.A. Cutaneous melanoma. Lancet 2023 402 10400 485 502 10.1016/S0140‑6736(23)00821‑8 37499671
    [Google Scholar]
  12. Sadeq M.A. Ashry M.H. Ghorab R.M.F. Afify A.Y. Causes of death among patients with cutaneous melanoma: A US population-based study. Sci. Rep. 2023 13 1 10257 10.1038/s41598‑023‑37333‑4 37355743
    [Google Scholar]
  13. Kim H.J. Kim Y.H. Molecular frontiers in melanoma: Pathogenesis, diagnosis, and therapeutic advances. Int. J. Mol. Sci. 2024 25 5 2984 10.3390/ijms25052984 38474231
    [Google Scholar]
  14. Wróblewska-Łuczka P. Cabaj J. Bargieł J. Łuszczki J.J. Anticancer effect of terpenes: Focus on malignant melanoma. Pharmacol. Rep. 2023 75 5 1115 1125 10.1007/s43440‑023‑00512‑1 37515699
    [Google Scholar]
  15. Campagna R. Bacchetti T. Salvolini E. Pozzi V. Molinelli E. Brisigotti V. Sartini D. Campanati A. Ferretti G. Offidani A. Emanuelli M. Paraoxonase-2 silencing enhances sensitivity of A375 melanoma cells to treatment with cisplatin. Antioxidants 2020 9 12 1238 10.3390/antiox9121238 33297311
    [Google Scholar]
  16. Trager M.H. Geskin L.J. Samie F.H. Liu L. Biomarkers in melanoma and non‐melanoma skin cancer prevention and risk stratification. Exp. Dermatol. 2022 31 1 4 12 10.1111/exd.14114 32415889
    [Google Scholar]
  17. Di Raimondo C. Lozzi F. Di Domenico P.P. Campione E. Bianchi L. The diagnosis and management of cutaneous metastases from melanoma. Int. J. Mol. Sci. 2023 24 19 14535 10.3390/ijms241914535 37833981
    [Google Scholar]
  18. Villani A. Potestio L. Fabbrocini G. Troncone G. Malapelle U. Scalvenzi M. The treatment of advanced melanoma: Therapeutic update. Int. J. Mol. Sci. 2022 23 12 6388 10.3390/ijms23126388 35742834
    [Google Scholar]
  19. Pham J.P. Joshua A.M. da Silva I.P. Dummer R. Goldinger S.M. Chemotherapy in cutaneous melanoma: Is there still a role? Curr. Oncol. Rep. 2023 25 6 609 621 10.1007/s11912‑023‑01385‑6 36988735
    [Google Scholar]
  20. Swetter S.M. Thompson J.A. Albertini M.R. Barker C.A. Baumgartner J. Boland G. Chmielowski B. DiMaio D. Durham A. Fields R.C. Fleming M.D. Galan A. Gastman B. Grossmann K. Guild S. Holder A. Johnson D. Joseph R.W. Karakousis G. Kendra K. Lange J.R. Lanning R. Margolin K. Olszanski A.J. Ott P.A. Ross M.I. Salama A.K. Sharma R. Skitzki J. Sosman J. Wuthrick E. McMillian N.R. Engh A.M. NCCN guidelines® insights: Melanoma: Cutaneous, version 2.2021: Featured updates to the NCCN guidelines. J. Natl. Compr. Canc. Netw. 2021 19 4 364 376 10.6004/jnccn.2021.0018 33845460
    [Google Scholar]
  21. Georgieva M. Tzankova D. Mateev E. Angelov B. Kondeva-Burdina M. Momekov G. Tzankova V. Zlatkov A. In silico and in vitro determination of antiproliferative activity of series N-pyrrolyl hydrazide-hydrazones and evaluation of their effects on isolated rat mycrosomes and hepatocytes. Anticancer. Agents Med. Chem. 2023 23 3 346 359 10.2174/1871520622666220701114306 35786338
    [Google Scholar]
  22. Lindgren E.B. de Brito M.A. Vasconcelos T.R.A. de Moraes M.O. Montenegro R.C. Yoneda J.D. Leal K.Z. Synthesis and anticancer activity of (E)-2-benzothiazole hydrazones. Eur. J. Med. Chem. 2014 86 12 16 10.1016/j.ejmech.2014.08.039 25147145
    [Google Scholar]
  23. Kaplánek R. Jakubek M. Rak J. Kejík Z. Havlík M. Dolenský B. Frydrych I. Hajdúch M. Kolář M. Bogdanová K. Králová J. Džubák P. Král V. Caffeine–hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells. Bioorg. Chem. 2015 60 19 29 10.1016/j.bioorg.2015.03.003 25912310
    [Google Scholar]
  24. El-Faham A. Farooq M. Khattab S. Abutaha N. Wadaan M. Ghabbour H. Fun H.K. Synthesis, characterization, and anti-cancer activity of some new N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones derivatives. Molecules 2015 20 8 14638 14655 10.3390/molecules200814638 26287132
    [Google Scholar]
  25. Page M.J. McKenzie J.E. Bossuyt P.M. Boutron I. Hoffmann T.C. Mulrow C.D. Shamseer L. Tetzlaff J.M. Akl E.A. Brennan S.E. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Pan Am J. Public. Health. 2022 46 e112 e112
    [Google Scholar]
  26. Cohen J. Weighted kappa: Nominal scale agreement provision for scaled disagreement or partial credit. Psychol. Bull. 1968 70 4 213 220 10.1037/h0026256 19673146
    [Google Scholar]
  27. Shea B.J. Reeves B.C. Wells G. Thuku M. Hamel C. Moran J. Moher D. Tugwell P. Welch V. Kristjansson E. Henry D.A. AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017 358 j4008 10.1136/bmj.j4008 28935701
    [Google Scholar]
  28. Liu L. Li Y. Xiong Y. Cavallucci D. A new function-based patent knowledge retrieval tool for conceptual design of innovative products. Comput. Ind. 2020 115 103154 10.1016/j.compind.2019.103154
    [Google Scholar]
  29. Zhang L. Liu W. Chen Y. Yue X. Reliable multi-view deep patent classification. Mathematics 2022 10 23 4545 10.3390/math10234545
    [Google Scholar]
  30. Demurtas M. Baldisserotto A. Lampronti I. Moi D. Balboni G. Pacifico S. Vertuani S. Manfredini S. Onnis V. Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones. Bioorg. Chem. 2019 85 568 576 10.1016/j.bioorg.2019.02.007 30825715
    [Google Scholar]
  31. Maltarollo V.G. Resende M.F. Kronenberger T. Lino C.I. Sampaio M.C.P.D. Pitta M.G.R. Rêgo M.J.B.M. Labanca R.A. Oliveira R.B. In vitro and in silico studies of antioxidant activity of 2-thiazolylhydrazone derivatives. J. Mol. Graph. Model. 2019 86 106 112 10.1016/j.jmgm.2018.10.007 30347318
    [Google Scholar]
  32. Abbas S.H. Abd El-Hafeez A.A. Shoman M.E. Montano M.M. Hassan H.A. New quinoline/chalcone hybrids as anti-cancer agents: Design, synthesis, and evaluations of cytotoxicity and PI3K inhibitory activity. Bioorg. Chem. 2019 82 360 377 10.1016/j.bioorg.2018.10.064 30428415
    [Google Scholar]
  33. Khalil O.M. Gedawy E.M. El-Malah A.A. Adly M.E. Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile. Bioorg. Chem. 2019 83 262 276 10.1016/j.bioorg.2018.10.058 30391699
    [Google Scholar]
  34. Abo-Ashour M.F. Eldehna W.M. Nocentini A. Bonardi A. Bua S. Ibrahim H.S. Elaasser M.M. Kryštof V. Jorda R. Gratteri P. Abou-Seri S.M. Supuran C.T. 3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights. Eur. J. Med. Chem. 2019 184 111768 10.1016/j.ejmech.2019.111768 31629164
    [Google Scholar]
  35. Kazan F. Yagci Z.B. Bai R. Ozkirimli E. Hamel E. Ozkirimli S. Synthesis and biological evaluation of indole-2-carbohydrazides and thiazolidinyl-indole-2-carboxamides as potent tubulin polymerization inhibitors. Comput. Biol. Chem. 2019 80 512 523 10.1016/j.compbiolchem.2019.05.002 31185422
    [Google Scholar]
  36. Katariya K.D. Shah S.R. Reddy D. Anticancer, antimicrobial activities of quinoline based hydrazone analogues: Synthesis, characterization and molecular docking. Bioorg. Chem. 2020 94 103406 10.1016/j.bioorg.2019.103406 31718889
    [Google Scholar]
  37. Tripathi K. Rai A. Sonkar A.K. Yashaswee S. Trigun S.K. Mishra L. Synthesis, photo-physical, computational and invitro cytotoxic studies of 4-((E)-2-benzylidenehydrazinyl)benzonitrile derivatives. J. Photochem. Photobiol. Chem. 2019 375 252 260 10.1016/j.jphotochem.2019.02.013
    [Google Scholar]
  38. Sâmia L.B.P. Parrilha G.L. Bertoli A.C. Duarte H.A. Speziali N.L. Teixeira S.F. Kawamura B. Ferreira A.K. Beraldo H. Investigation on the cytotoxic effects of nitrogen-mustard-derived Schiff bases. Studies on the reactivity of the N-mustard pharmacophoric group. J. Mol. Struct. 2019 1178 274 284 10.1016/j.molstruc.2018.10.029
    [Google Scholar]
  39. Sultana F. Saifi M.A. Syed R. Mani G.S. Shaik S.P. Osas E.G. Godugu C. Shahjahan S. Kamal A. Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents. New J. Chem. 2019 43 18 7150 7161 10.1039/C8NJ06517A
    [Google Scholar]
  40. Baldisserotto A. Demurtas M. Lampronti I. Tacchini M. Moi D. Balboni G. Vertuani S. Manfredini S. Onnis V. In-vitro evaluation of antioxidant, antiproliferative and photo-protective activities of benzimidazolehydrazone derivatives. Pharmaceuticals 2020 13 4 68 10.3390/ph13040068 32326658
    [Google Scholar]
  41. Elbastawesy M.A.I. Ramadan M. El-Shaier Y.A.M.M. Aly A.A. Abuo-Rahma G.E.D.A. Arylidenes of Quinolin-2-one scaffold as Erlotinib analogues with activities against leukemia through inhibition of EGFR TK/ STAT-3 pathways. Bioorg. Chem. 2020 96 103628 10.1016/j.bioorg.2020.103628 32062064
    [Google Scholar]
  42. Helwa A.A. El-Dydamony N.M. Radwan R.A. Abdelraouf S.M. Abdelnaby R.M. Novel antiproliferative agents bearing morpholinopyrimidine scaffold as PI3K inhibitors and apoptosis inducers; design, synthesis and molecular docking. Bioorg. Chem. 2020 102 104051 10.1016/j.bioorg.2020.104051 32659486
    [Google Scholar]
  43. Chang S. Qin D. Wang L. Zhang M. Yan R. Zhao C. Preparation of novel cinnamaldehyde derivative–BSA nanoparticles with high stability, good cell penetrating ability, and promising anticancer activity. Colloids Surf. A Physicochem. Eng. Asp. 2021 624 126765 10.1016/j.colsurfa.2021.126765
    [Google Scholar]
  44. Mohammed E.Z. Mahmoud W.R. George R.F. Hassan G.S. Omar F.A. Georgey H.H. Synthesis, in vitro anticancer activity and in silico studies of certain pyrazole-based derivatives as potential inhibitors of cyclin dependent kinases (CDKs). Bioorg. Chem. 2021 116 105347 10.1016/j.bioorg.2021.105347 34555628
    [Google Scholar]
  45. Abou-Seri S.M. Eissa A.A.M. Behery M.G.M. Omar F.A. Synthesis, in vitro anticancer activity and in silico studies of certain isoxazole-based carboxamides, ureates, and hydrazones as potential inhibitors of VEGFR2. Bioorg. Chem. 2021 116 105334 10.1016/j.bioorg.2021.105334 34534755
    [Google Scholar]
  46. Oliveira A.R. dos Santos F.A. Ferreira L.P.L. Pitta M.G.R. Silva M.V.O. Cardoso M.V.O. Pinto A.F. Marchand P. de Melo Rêgo M.J.B. Leite A.C.L. Synthesis, anticancer activity and mechanism of action of new phthalimido-1,3-thiazole derivatives. Chem. Biol. Interact. 2021 347 109597 10.1016/j.cbi.2021.109597 34303695
    [Google Scholar]
  47. Tumosienė I. Jonuškienė I. Kantminienė K. Mickevičius V. Petrikaitė V. Novel N-substituted amino acid hydrazone-isatin derivatives: Synthesis, antioxidant activity, and anticancer activity in 2D and 3D models in vitro. Int. J. Mol. Sci. 2021 22 15 7799 7821 10.3390/ijms22157799 34360565
    [Google Scholar]
  48. Ribeiro N. Bulut I. Pósa V. Sergi B. Sciortino G. Pessoa J.C. Maia L.B. Ugone V. Garribba E. Enyedy É.A. Acilan C. Correia I. Solution chemical properties and anticancer potential of 8-hydroxyquinoline hydrazones and their oxidovanadium(IV) complexes. J. Inorg. Biochem. 2022 235 111932 10.1016/j.jinorgbio.2022.111932 35940023
    [Google Scholar]
  49. Samir M. Ramadan M. Abdelrahman M.H. Abdelbaset M.S. Abourehab M.A.S. Abdel-Aziz M. Abuo-Rahma G.E.D.A. 3,7-bis-benzylidene hydrazide ciprofloxacin derivatives as promising antiproliferative dual TOP I & TOP II isomerases inhibitors. Bioorg. Chem. 2021 110 104698 10.1016/j.bioorg.2021.104698 33676043
    [Google Scholar]
  50. Šermukšnytė A. Kantminienė K. Jonuškienė I. Tumosienė I. Petrikaitė V. The effect of 1,2,4-Triazole-3-thiol derivatives bearing hydrazone moiety on cancer cell migration and growth of melanoma, breast, and pancreatic cancer spheroids. Pharmaceuticals 2022 15 8 1026 10.3390/ph15081026 36015174
    [Google Scholar]
  51. Ismael A.S. Amin N.H. Elsaadi M.T. Abdel-Rahman H.M. Design, synthesis and mechanistic studies of novel imidazo[1,2-a]pyridines as anticancer agents. Bioorg. Chem. 2022 128 106042 10.1016/j.bioorg.2022.106042 35878430
    [Google Scholar]
  52. Tasneem S. Sheikh K.A. Naematullah M. Mumtaz Alam M. Khan F. Garg M. Amir M. Akhter M. Amin S. Haque A. Shaquiquzzaman M. Synthesis, biological evaluation and docking studies of methylene bearing cyanopyrimidine derivatives possessing a hydrazone moiety as potent Lysine specific demethylase-1 (LSD1) inhibitors: A promising anticancer agents. Bioorg. Chem. 2022 126 105885 10.1016/j.bioorg.2022.105885 35636128
    [Google Scholar]
  53. Bergamini F.R.G. Nunes J.H.B. Manzano C.M. de Carvalho M.A. Ribeiro M.A. Ruiz A.L.T.G. de Carvalho J.E. Lustri W.R. de Paiva R.E.F. Portes M.C. da Costa Ferreira A.M. Corbi P.P. Investigating the antiproliferative activities of new CuII complexes with pyridine hydrazone derivatives of nalidixic acid. J. Inorg. Biochem. 2022 234 111881 10.1016/j.jinorgbio.2022.111881 35691262
    [Google Scholar]
  54. Tawfik H.O. Petreni A. Supuran C.T. El-Hamamsy M.H. Discovery of new carbonic anhydrase IX inhibitors as anticancer agents by toning the hydrophobic and hydrophilic rims of the active site to encounter the dual-tail approach. Eur. J. Med. Chem. 2022 232 114190 10.1016/j.ejmech.2022.114190 35182815
    [Google Scholar]
  55. Sajjan V.P. Anigol L.B. Gurubasavaraj P.M. Patil D. Patil P.S. Gummagol N.B. Quah C.K. Wong Q.A. Celik I. New2-((2-(2,4-dinitrophenyl)hydrazineeylidene) derivatives: Design, synthesis, in silico, and in vitro anticancer studies. J. Biomol. Struct. Dyn. 2023 41 21 11681 11699 10.1080/07391102.2022.2163424 36602778
    [Google Scholar]
  56. Garberová M. Potočňák I. Tvrdoňová M. Bago-Pilátová M. Bekešová S. Kudličková Z. Samoľová E. Kešeľáková A. Elečko J. Vilková M. Spectral, structural, and pharmacological studies of perillaldehyde and myrtenal based benzohydrazides. J. Mol. Struct. 2023 1271 134112 10.1016/j.molstruc.2022.134112
    [Google Scholar]
  57. Ahmed R.F. Mahmoud W.R. Abdelgawad N.M. Fouad M.A. Said M.F. Exploring novel anticancer pyrazole benzenesulfonamides featuring tail approach strategy as carbonic anhydrase inhibitors. Eur. J. Med. Chem. 2023 261 115805 10.1016/j.ejmech.2023.115805 37748386
    [Google Scholar]
  58. Gao Z. Chen Y. Nie Y. Chen K. Cao X. Ke S. Structural diversity-guided optimization of carbazole derivatives as potential cytotoxic agents. Front Chem. 2023 11 1104868 10.3389/fchem.2023.1104868 36742033
    [Google Scholar]
  59. Negru Apostol G. Ghinet A. Bîcu E. 7-Chloroquinolinehydrazones as first-in-class anticancer experimental drugs in the NCI-60 screen among different investigated series of aryl, quinoline, pyridine, benzothiazole and imidazolehydrazones. Pharmaceuticals 2023 16 5 691 10.3390/ph16050691 37242474
    [Google Scholar]
  60. Bora D. Sharma A. John S.E. Shankaraiah N. Development of hydrazide hydrazone-tethered combretastatin-oxindole derivatives as antimitotic agents. J. Mol. Struct. 2023 1275 134675 10.1016/j.molstruc.2022.134675
    [Google Scholar]
  61. Zubrickė I. Jonuškienė I. Kantminienė K. Tumosienė I. Petrikaitė V. Synthesis and in vitro evaluation as potential anticancer and antioxidant agents of diphenylamine-pyrrolidin-2-one-hydrazone derivatives. Int. J. Mol. Sci. 2023 24 23 16804 16823 10.3390/ijms242316804 38069128
    [Google Scholar]
  62. Ribeiro N. Bulut I. Sergi B. Pósa V. Spengler G. Sciortino G. André V. Ferreira L.P. Biver T. Ugone V. Garribba E. Costa-Pessoa J. Enyedy É.A. Acilan C. Correia I. Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes. Front Chem. 2023 11 1106349 10.3389/fchem.2023.1106349 37025548
    [Google Scholar]
  63. Abdel-Azziz I.A. Amin N.H. El-Saadi M.T. Abdel-Rahman H.M. Design, synthesis and mechanistic studies of benzophenones hydrazone derivatives as cathepsin inhibitors. J. Mol. Struct. 2023 1274 134583 10.1016/j.molstruc.2022.134583
    [Google Scholar]
  64. Gurubasavaraj P.M. Sajjan V.P. Muñoz-Flores B.M. Jiménez Pérez V.M. Patil D. Patil P.S. Gummagol N.B. Synthesis, structure–activity relationship studies using density functional theory and in silico molecular docking on substituted benzohydrazide derivatives. J. Mol. Struct. 2024 1299 137134 10.1016/j.molstruc.2023.137134
    [Google Scholar]
  65. Duarte A.C. Costa E.C. Filipe H.A.L. Saraiva S.M. Jacinto T. Miguel S.P. Ribeiro M.P. Coutinho P. Animal-derived products in science and current alternatives. Biomater. Adv. 2023 151 213428 213428 10.1016/j.bioadv.2023.213428 37146527
    [Google Scholar]
  66. Díaz L. Zambrano E. Flores M.E. Contreras M. Crispín J.C. Alemán G. Bravo C. Armenta A. Valdés V.J. Tovar A. Gamba G. Barrios-Payán J. Bobadilla N.A. Ethical considerations in animal research: The principle of 3R’s. Rev. Invest. Clin. 2021 73 4 199 209 10.24875/RIC.20000380 33090120
    [Google Scholar]
  67. Bédard P. Gauvin S. Ferland K. Caneparo C. Pellerin È. Chabaud S. Bolduc S. Innovative human three-dimensional tissue-engineered models as an alternative to animal testing. Bioengineering 2020 7 3 115 10.3390/bioengineering7030115 32957528
    [Google Scholar]
  68. eBioMedicine, The 3Rs of animal research. EBioMedicine 2022 76 103900 10.1016/j.ebiom.2022.103900
    [Google Scholar]
  69. Arruda I. Macedo B. Macedo J. Campos W. Araújo C. Gonsalves A. Preparation of hydrazone and N-acylhydrazone using commercial drugs as reagents: Practical classes for the synthesis of bioactive compounds [in Portuguese]. Química Nova 2020 43 642 648 10.21577/0100‑4042.20170497
    [Google Scholar]
  70. Ahmad S. Khan M. Shah M.I.A. Ali M. Alam A. Riaz M. Khan K.M. Synthetic transformation of 2-2-Fluoro[1,1′-biphenyl]-4-yl propanoic acid into hydrazide–hydrazone derivatives: In vitro urease inhibition and in silico study. ACS Omega 2022 7 49 45077 45087 10.1021/acsomega.2c05498 36530251
    [Google Scholar]
  71. Boudreau M.W. Tonogai E.J. Schane C.P. Xi M.X. Fischer J.H. Vijayakumar J. Ji Y. Tarasow T.M. Fan T.M. Hergenrother P.J. Dudek A.Z. The combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma. Melanoma Res. 2023 33 6 514 524 10.1097/CMR.0000000000000927 37738028
    [Google Scholar]
  72. Murugappan S. Dastari S. Jungare K. Barve N.M. Shankaraiah N. Hydrazide-hydrazone/hydrazone as enabling linkers in anti-cancer drug discovery: A comprehensive review. J. Mol. Struct. 2024 1307 138012 10.1016/j.molstruc.2024.138012
    [Google Scholar]
  73. Belyaeva E.R. Myasoedova Y.V. Ishmuratova N.M. Ishmuratov G.Y. Synthesis and biological activity of N-acylhydrazones. Russ. J. Bioorganic Chem. 2022 48 6 1123 1150 10.1134/S1068162022060085
    [Google Scholar]
  74. Valdez B.C. Yuan B. Murray D. Nieto Y. Popat U. Andersson B.S. Enhanced cytotoxicity of bisantrene when combined with venetoclax, panobinostat, decitabine and olaparib in acute myeloid leukemia cells. Leuk. Lymphoma 2022 63 7 1634 1644 10.1080/10428194.2022.2042689 35188042
    [Google Scholar]
  75. Verrills N.M. Murray H.C. Brzozowski J.S. Panicker N. Miller K. Messina M. Buckley B.J. Kelso M.J. Enjeti A.K. Preclinical evaluation of bisantrene as single agent and in combination with decitabine for acute myeloid leukemia. Blood 2023 142 Supplement 1 5773 5773 10.1182/blood‑2023‑188353
    [Google Scholar]
  76. Dey R. Vishwakarma K. Patel B. Vyas V.K. Bhatt H. Evolution of telomerase inhibitors: A review on key patents from 2015 to 2023. ChemistrySelect 2024 9 47 202404444 10.1002/slct.202404444
    [Google Scholar]
  77. Canaani J. Danylesko I. Shemtov N. Zlotnick M. Lozinsky K. Benjamini O. Yerushalmi R. Nagar M. Dor C. Shimoni A. Avigdor A. Nagler A. A phase II study of bisantrene in patients with relapsed/refractory acute myeloid leukemia. Eur. J. Haematol. 2021 106 2 260 266 10.1111/ejh.13544 33159365
    [Google Scholar]
  78. Yadav P. Yadav R. Jain S. Vaidya A. Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy. Chem. Biol. Drug Des. 2021 98 1 144 165 10.1111/cbdd.13860 33963665
    [Google Scholar]
  79. Danciu O.C. Holdhoff M. Peterson R.A. Fischer J.H. Liu L.C. Wang H. Venepalli N.K. Chowdhery R. Nicholas M.K. Russell M.J. Fan T.M. Hergenrother P.J. Tarasow T.M. Dudek A.Z. Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies. Br. J. Cancer 2023 128 5 783 792 10.1038/s41416‑022‑02089‑7 36470974
    [Google Scholar]
  80. Loo Y.S. Zahid N.I. Madheswaran T. Ikeno S. Nurdin A. Mat Azmi I.D. Coencapsulation of gemcitabine and thymoquinone in citrem–phosphatidylcholine hexosome nanocarriers improves in vitro cellular uptake in breast cancer cells. Mol. Pharm. 2023 20 9 4611 4628 10.1021/acs.molpharmaceut.3c00333 37587099
    [Google Scholar]
  81. Wróblewska-Łuczka P. Grabarska A. Góralczyk A. Marzęda P. Łuszczki J.J. Fraxetin interacts additively with cisplatin and mitoxantrone, antagonistically with docetaxel in various human melanoma cell lines-an isobolographic analysis. Int. J. Mol. Sci. 2022 24 1 212 10.3390/ijms24010212 36613654
    [Google Scholar]
  82. Wróblewska-Łuczka P. Grabarska A. Florek-Łuszczki M. Plewa Z. Łuszczki J.J. Synergy, additivity, and antagonism between cisplatin and selected coumarins in human melanoma cells. Int. J. Mol. Sci. 2021 22 2 537 10.3390/ijms22020537 33430369
    [Google Scholar]
  83. Krewski D. Andersen M.E. Tyshenko M.G. Krishnan K. Hartung T. Boekelheide K. Wambaugh J.F. Jones D. Whelan M. Thomas R. Yauk C. Barton-Maclaren T. Cote I. Toxicity testing in the 21st century: Progress in the past decade and future perspectives. Arch. Toxicol. 2020 94 1 1 58 10.1007/s00204‑019‑02613‑4 31848664
    [Google Scholar]
  84. Min H.Y. Lee H.Y. Molecular targeted therapy for anticancer treatment. Exp. Mol. Med. 2022 54 10 1670 1694 10.1038/s12276‑022‑00864‑3 36224343
    [Google Scholar]
  85. Chaudhry G. Zeenia; Safdar, N.; Begum, S.; Akim, A.M.; Sung, Y.Y.; Muhammad, T.S.T. Cytotoxicity assays for cancer drug screening: Methodological insights and considerations for reliable assessment in drug discovery. Braz. J. Biol. 2024 84 284409 10.1590/1519‑6984.284409 39699393
    [Google Scholar]
  86. Bahar E. Yoon H. Modeling and predicting the cell migration properties from scratch wound healing assay on cisplatin-resistant ovarian cancer cell lines using artificial neural network. Health Care 2021 9 7 911 10.3390/healthcare9070911 34356289
    [Google Scholar]
  87. Roney M. Mohd Aluwi M.F.F. The importance of in-silico studies in drug discovery. Intelligent Pharmacy 2024 2 4 578 579 10.1016/j.ipha.2024.01.010
    [Google Scholar]
  88. Guha R. On exploring structure-activity relationships. Methods Mol. Biol. 2013 993 81 94 10.1007/978‑1‑62703‑342‑8_6 23568465
    [Google Scholar]
  89. Yadav G. Ganguly S. Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review. Eur. J. Med. Chem. 2015 97 419 443 10.1016/j.ejmech.2014.11.053 25479684
    [Google Scholar]
  90. Southan C. Examples of SAR-centric patent mining using open resources. Comprehensive Medicinal Chemistry III; Elsevier 2017 464 487 10.1016/B978‑0‑12‑409547‑2.13814‑4
    [Google Scholar]
  91. Hemmerich J. Ecker G.F. In silico toxicology: From structure–activity relationships towards deep learning and adverse outcome pathways. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2020 10 4 1475 10.1002/wcms.1475 35866138
    [Google Scholar]
  92. Batool M. Ahmad B. Choi S. A structure-based drug discovery paradigm. Int. J. Mol. Sci. 2019 20 11 2783 10.3390/ijms20112783 31174387
    [Google Scholar]
  93. Blagosklonny M.V. Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells. Oncotarget 2023 14 1 193 206 10.18632/oncotarget.28382 36913303
    [Google Scholar]
  94. Da Silva R.C.D.S. Simon N.A. Dos Santos A.A. Olegário G.D.M. Da Silva J.F. Sousa N.O. Corbacho M.A.T. de Melo F.F. Personalized medicine: Clinical oncology on molecular view of treatment. World J. Clin. Oncol. 2024 15 8 992 1001 10.5306/wjco.v15.i8.992 39193152
    [Google Scholar]
  95. Hassan O.M. Razzak Mahmood A.A. Hamzah A.H. Tahtamouni L.H. Design, synthesis, and molecular docking studies of 5‐bromoindole‐2‐carboxylic acid hydrazone derivatives: In vitro anticancer and VEGFR‐2 inhibitory effects. ChemistrySelect 2022 7 46 202203726 10.1002/slct.202203726
    [Google Scholar]
  96. Erdönmez B. Altıntop M.D. Akalın Çiftçi G. Özdemir A. Ece A. Design, synthesis, and evaluation of a new series of hydrazones as small-molecule Akt inhibitors for NSCLC therapy. ACS Omega 2023 8 22 20056 20065 10.1021/acsomega.3c02331 37305321
    [Google Scholar]
  97. Brogyányi T. Kaplánek R. Kejík Z. Hosnedlová B. Antonyová V. Abramenko N. Veselá K. Martásek P. Vokurka M. Richardson D.R. Jakubek M. Azulene hydrazide-hydrazones for selective targeting of pancreatic cancer cells. Biomed. Pharmacother. 2022 155 113736 10.1016/j.biopha.2022.113736 36156366
    [Google Scholar]
  98. Lai Y. Chu X. Di L. Gao W. Guo Y. Liu X. Lu C. Mao J. Shen H. Tang H. Xia C.Q. Zhang L. Ding X. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development. Acta Pharm. Sin. B 2022 12 6 2751 2777 10.1016/j.apsb.2022.03.009 35755285
    [Google Scholar]
  99. Passannante R. Gómez-Vallejo V. Sagartzazu-Aizpurua M. Vignau Arsuaga L. Marco-Moreno P. Aldanondo G. Vallejo-Illarramendi A. Aguiar P. Cossío U. Martín A. Bergare J. Kingston L. Elmore C.S. Morcillo M.A. Ferrón P. Aizpurua J.M. Llop J. Pharmacokinetic evaluation of new drugs using a multi-labelling approach and PET imaging: Application to a drug candidate with potential application in neuromuscular disorders. Biomedicines 2023 11 2 253 10.3390/biomedicines11020253 36830793
    [Google Scholar]
  100. Zettler M.E. Dose optimization of targeted therapies for oncologic indications. Cancers 2024 16 12 2180 10.3390/cancers16122180 38927886
    [Google Scholar]
  101. Davis R.L. Mechanism of action and target identification: A matter of timing in drug discovery. iScience 2020 23 9 101487 10.1016/j.isci.2020.101487 32891054
    [Google Scholar]
  102. Lange S. Inal J.M. Animal models of human disease 2.0. Int. J. Mol. Sci. 2024 25 24 13743 10.3390/ijms252413743 39769507
    [Google Scholar]
  103. Adebayo G. Ayanda O.I. Rottmann M. Ajibaye O.S. Oduselu G. Mulindwa J. Ajani O.O. Aina O. Mäser P. Adebiyi E. The importance of Murine models in determining in vivo pharmacokinetics, safety, and efficacy in antimalarial drug discovery. Pharmaceuticals 2025 18 3 424 10.3390/ph18030424 40143200
    [Google Scholar]
  104. Mukherjee P. Roy S. Ghosh D. Nandi S.K. Role of animal models in biomedical research: A review. Lab. Anim. Res. 2022 38 1 18 10.1186/s42826‑022‑00128‑1 35778730
    [Google Scholar]
  105. Richards J.R. Yoo J.H. Shin D. Odelberg S.J. Mouse models of uveal melanoma: Strengths, weaknesses, and future directions. Pigment Cell Melanoma Res. 2020 33 2 264 278 10.1111/pcmr.12853 31880399
    [Google Scholar]
  106. Angelova V.T. Pencheva T. Vassilev N. K-Yovkova, E.; Mihaylova, R.; Petrov, B.; Valcheva, V. Development of new antimycobacterial sulfonyl hydrazones and 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives. Antibiotics 2022 11 5 562 10.3390/antibiotics11050562 35625207
    [Google Scholar]
  107. Babalola S. Igie N. Odeyemi I. Molecular docking, drug-likeness analysis, in silico pharmacokinetics, and toxicity studies of p-nitrophenyl hydrazones as anti-inflammatory compounds against COX-2, 5-LOX, and H+/K+ ATPase. Pharmaceutical Fronts 2022 4 4 e250 e266 10.1055/s‑0042‑1759688
    [Google Scholar]
  108. Sadee W. Wang D. Hartmann K. Toland A.E. Pharmacogenomics: Driving personalized medicine. Pharmacol. Rev. 2023 75 4 789 814 10.1124/pharmrev.122.000810 36927888
    [Google Scholar]
  109. Akbar S. Setia T. Das S. Kumari S. Rahaman S.B. Wasim M. Ahmed B. Dewangan R.P. Design, synthesis, and evaluation of 1,4-benzodioxane-hydrazone derivatives as potential therapeutics for skin cancer: in silico, in vitro, and in vivo studies. Bioorg. Chem. 2025 160 108449 10.1016/j.bioorg.2025.108449 40220711
    [Google Scholar]
  110. Ibraheem H.H. Queen B.K. Al-Sabti M.D. Issa A.A. Al-Majedy Y.K. Jabir M.S. Sulaiman G.M. Hasoon B.A. Eshaq M.M. Jawad K.H. Jawad S.F. Fawzi H.A. Shuaib M. Najm M.A.A. Swelum A.A. Insights into the pharmaceutical properties and in silico study of novel hydrazone derivatives. Sci. Rep. 2024 14 1 29912 10.1038/s41598‑024‑81555‑z 39622881
    [Google Scholar]
  111. Chitale S. Lawler C. Macfarlane S. Understanding the basics of patenting. Nat. Biotechnol. 2020 38 3 263 270 10.1038/s41587‑020‑0447‑x 32132682
    [Google Scholar]
  112. Zimmerling A. Chen X. Innovation and possible long-term impact driven by COVID-19: Manufacturing, personal protective equipment and digital technologies. Technol. Soc. 2021 65 101541 10.1016/j.techsoc.2021.101541 36540655
    [Google Scholar]
  113. COVID-19: Evaluation of therapeutic agents – COVID-19 Core Protocol 2020 Available from: https://www.who.int/publications/i/item/covid-19-core-protocol
  114. Moore T.J. Zhang C. Anderson G.S. Alexander E.T. Cahan R.S. Woodcock J. Estimated costs of pivotal trials for novel therapeutic agents approved by the US Food and Drug Administration, 2015–2016. JAMA Intern. Med. 2020 180 1041 1048 10.1001/jama.2020.1166 30264133
    [Google Scholar]
  115. Bailey C. Black J.R.M. Swanton C. Cancer research: The lessons to learn from COVID-19. Cancer Discov. 2020 10 9 1263 1266 10.1158/2159‑8290.CD‑20‑0823 32669285
    [Google Scholar]
  116. Daizadeh I. The impact of US medical product regulatory complexity on innovation: Preliminary evidence of interdependence, early acceleration, and subsequent inversion. arXiv 2022 10.48550/ARXIV.2211.12998
    [Google Scholar]
  117. Ovcharenko D. Mukhin D. Ovcharenko G. Alternative cancer therapeutics: Unpatentable compounds and their potential in oncology. Pharmaceutics 2024 16 9 1237 10.3390/pharmaceutics16091237 39339273
    [Google Scholar]
  118. Schmitt V.J. Denter N.M. Modeling an indicator for statutory patent novelty. World Pat. Inf. 2024 78 102283 102283 10.1016/j.wpi.2024.102283
    [Google Scholar]
  119. Dai R. Watal J. Product patents and access to innovative medicines. Soc. Sci. Med. 2021 291 114479 10.1016/j.socscimed.2021.114479 34700119
    [Google Scholar]
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