Synthesis and Evaluation of Novel Metacetamol Derivatives with Hydrazone Moiety as Anticancer and Antimicrobial Agents

Şenkardeş S., Atlıhan İ., Çayır E., Mega Tiber P., Orun O., Nigiz Ş., ...More

Chemistry and Biodiversity, vol.20, no.8, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 8
  • Publication Date: 2023
  • Doi Number: 10.1002/cbdv.202300766
  • Journal Name: Chemistry and Biodiversity
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Antimicrobial, cancer, hydrazones, metacetamol, molecular docking
  • Hacettepe University Affiliated: Yes


By exploiting the wide biological potential of the hydrazone scaffold, a series of hydrazone derivatives were synthesized, starting from N-(3-hydroxyphenyl)acetamide (metacetamol). The structures of the compounds were determined using IR, 1H and 13C-NMR, and mass spectroscopic methods. The obtained molecules (3 a–j) were evaluated for their anticancer potential against MDA-MB-231 and MCF-7 breast cancer cell lines. According to the CCK-8 assay, all tested compounds showed moderate to potent anticancer activity. Among them, N-(3-(2-(2-(4-nitrobenzylidene)hydrazinyl)-2-oxoethoxy)phenyl)acetamide (3 e) was found to be the most effective derivative with an IC50 value of 9.89 μM against MDA-MB-231 cell lines. This compound was further tested for its potential effects on the apoptotic pathway. Molecular docking studies was also carried out for 3 e in the colchicine binding pocket of tubulin. Additionally, compound 3 e also demonstrated effective antifungal activity, particularly against Candida krusei (MIC=8 μg/ml), indicating that nitro group at the 4th position of the phenyl ring was the most preferable substituent for both cytotoxic and antimicrobial activity. Our preliminary findings suggest that compound 3 e could be exploited as a leading structure for further anticancer and antifungal drug development.