Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1,2,4-triazole

PLoS One. 2022 Dec 15;17(12):e0278027. doi: 10.1371/journal.pone.0278027. eCollection 2022.

Abstract

Novel azomethines derived from acefylline tethered triazole hybrids (7a-k) have been synthesized and evaluated against human liver cancer cell line (Hep G2) using MTT assay. The synthesized series of azomethines exhibited promising efficacy against liver cancer cell line. Screening of the synthesized series identified compound 7d with the least cell viability value (11.71 ± 0.39%) as the most potent anticancer agent in contrast to the reference drug acefylline (cell viability = 80 ± 3.87%). In this study, the potentials of the novel agents (7a-k) to inhibit liver cancer proteins were assessed. Subsequently, the structure-activity relationship of the potential drug candidates was assessed via ADME/T molecular screening. The cytotoxic potential of these derivatives was also investigated by hemolysis and thrombolysis. Their hemolytic and thrombolytic studies showed that all of these drugs had very low cytotoxicity and moderate clot lysis activity. Compound 7g (0.26% hemolysis) and 7k (52.1% clot lysis) were the least toxic and moderate thrombolytic agents respectively.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Drug Repositioning
  • Drug Screening Assays, Antitumor
  • Hemolysis
  • Humans
  • Liver Neoplasms*
  • Molecular Structure
  • Structure-Activity Relationship
  • Triazoles / pharmacology

Substances

  • 1,2,4-triazole
  • azomethine
  • acefylline
  • Triazoles
  • Antineoplastic Agents

Grants and funding

The author(s) received no specific funding for this work.