In-silico Molecular Docking ADME Study and Synthesis of Eugenol Derivatives as Antiproliferative

Abstract

The use of semisynthetic alterations to natural materials has provided us with several anticancer medications.The current study involves the synthetic modification of eugenol, a natural substance, to create novel anticancer drugs.The ultimate compounds were verified for their structure using NMR, IR, and mass methods.Based on the cytotoxicity data, compound 17 containing morpholine was identified as the most potent cytotoxic agent, exhibiting IC50 values of 1.71 M (MCF-7), 1.84 M (SKOV3), and 1.1 M (PC-3).Additionally, it demonstrated inhibitory activity against thymidylate synthase (TS) with an IC50 value of 0.81 M.Subsequent cellular investigations demonstrated that compound 17 has the ability to trigger apoptosis and halt the cell cycle specifically during the S phase in PC-3 cancer.Based on the docking investigation, compound 17 is very likely to be a transition state inhibitor, as it exhibited a comparable interaction to 5-fluorouracil.The results obtained from docking and biological assessment are supported by in silico pharmacokinetics and DFT computational investigations, which indicate a favorable pharmacokinetic profile for the medicine to be administered orally.Compound 17 shown potential as a promising inhibitor of thymidylate synthase (TS), effectively inhibiting DNA synthesis and thus reducing DNA damage in prostate cancer cells.