New Natural Eugenol Derivatives As Antiproliferative Agents: Synthesis, Biological Evaluation, and Computational Studies

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Jun 5

PMID 37273621

Authors

Syed Nazreen

Serag Eldin I Elbehairi

Azizah M Malebari

Nuha Alghamdi

Reem F Alshehri

Ali A Shati

Nada M Ali

Mohammad Y Alfaifi

Ahmed A Elhenawy

Mohammad Mahboob Alam

Affiliations

Soon will be listed here.

Abstract

Semisynthetic modifications of natural products have bestowed us with many anticancer drugs. In the present work, a natural product, eugenol, has been modified synthetically to generate new anticancer agents. The final compounds were structurally confirmed by NMR, IR, and mass techniques. From the cytotoxicity results, compound bearing morpholine was found to be the most active cytotoxic agent with IC 1.71 (MCF-7), 1.84 (SKOV3), and 1.1 μM (PC-3) and a thymidylate synthase (TS) inhibitor with an IC of 0.81 μM. Further cellular studies showed that compound could induce apoptosis and arrest the cell cycle at the S phase in PC-3 carcinoma. The docking study strongly favors compound to be a TS inhibitor as it displayed a similar interaction to 5-fluorouracil. The in silico pharmacokinetics and DFT computational studies support the results obtained from docking and biological evaluation and displayed favorable pharmacokinetic profile for a drug to be orally available. Compound was found to be a promising TS inhibitor which could suppress DNA synthesis and consequently DNA damage in prostate cancer cells.

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