Synthesis, Characterization and In Vitro & In Silico Biological Evaluation of New Mannich-Based Rhodanine and Thiazolidine-2,4-Dione Derivatives as Potential Anti-Lung Cancer Agents

In this study, ten new rhodanine and thiazolidine-2,4-dione derivatives based on Mannich-modified vanillin were synthesized, characterized, and evaluated for their anticancer potential against A549 lung cancer and BEAS-2B normal cells. Among them, compound 5c exhibited the most potent anticancer activity, with an IC50 of 2.43 µM and a selectivity index of 10.91, showing higher selectivity than the reference drug sorafenib. Molecular docking studies suggested 5c as a strong potential EGFR inhibitor, supported by a docking score of -9.827 kcal/mol and key interactions with residues such as Met-793, Leu-788, and Phe-856. Molecular dynamics simulations further confirmed the stability of the 5c-EGFR complex. ADMET predictions indicated favorable pharmacokinetic and safety profiles for 5c, including high permeability, oral absorption, and no significant toxicity. These findings highlight 5c as a promising lead compound for targeted lung cancer therapy, warranting further preclinical studies.

Publication History

Received: 27 December 2024

Accepted after revision: 17 February 2025

Accepted Manuscript online:
17 February 2025