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Synthesis, molecular docking, ADMET evaluation and in vitro cytotoxic activity evaluation on RD and L20B cell lines of 3-substituted 5,5-diphenylimidazolidine-2,4-dione derivatives.

Walid GuerrabJihane AkacharMeryem El JemliAbdul-Malik AbuduniaRachida OuaabouKatim AlaouiAzeddine IbrahimiYoussef Ramli
Published in: Journal of biomolecular structure & dynamics (2022)
Hydantoins comprise an important class of compounds which have long attracted attention due to their remarkable biological and pharmacological properties including antitumor and antiviral activities. As a continuation of our studies on hydantoins derivatives we report the successful synthesis of hydantoins derivatives. These synthesized compounds were evaluated for their cytotoxic activity against Vero cells L20B (African green monkey kidney cell line) and Human Rhabdomyosarcoma RD cell lines using methotrexate drug ( MTX ) as a reference drug in cytotoxic activity studies. The percentage of the cell line viability was carried out by using Trypan blue dye exclusion method. The tested compounds showed equipotent cytotoxicity effect against Vero cells (L20B) and a moderate effect against Human Rhabdomyosarcoma ( RD ) cell lines. These results exhibited better activity for 4a-b compounds than the reference drug methotrexate (MTX). Molecular docking studies indicated that the synthesized compounds are suitable inhibitors of humain dihydrofolate reductase (DHFR) enzyme, which may explain the high antiproliferative activity.Communicated by Ramaswamy H. Sarma.
Keyphrases
  • molecular docking
  • molecular dynamics simulations
  • induced apoptosis
  • endothelial cells
  • cell cycle arrest
  • emergency department
  • cell death
  • case control
  • adverse drug
  • endoplasmic reticulum stress
  • signaling pathway