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Synlett
DOI: 10.1055/a-2541-1072
DOI: 10.1055/a-2541-1072
letter
Small Molecules in Medicinal Chemistry
Synthesis, Characterization and In Vitro and In Silico Biological Evaluation of New Mannich-Based Rhodanine and Thiazolidine-2,4-dione Derivatives as Potential Anti-Lung-Cancer Agents
Abstract
In this study, 10 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 epidermal growth factor receptor (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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2541-1072.
The experimental sections for the chemistry, biological activity and computational
studies, along with the experimental data for the remaining compounds, are available
in the supporting material. This includes the spectral data for all compounds, inhibition
graphics and toxicity prediction reports.
- Supporting Information
Publication History
Received: 27 December 2024
Accepted after revision: 17 February 2025
Accepted Manuscript online:
17 February 2025
Article published online:
08 April 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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