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DOI: 10.1055/a-2541-1072
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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

Şeyma Ateşoğlu
a   Bezmialem Vakif University, Institute of Health Sciences, Department of Biotechnology, 34093 Fatih, Istanbul, Türkiye
b   Bezmialem Vakif University, Faculty of Medicine, Department of Medical Biology, 34093 Fatih, Istanbul, Türkiye
,
Furkan Çakır
c   Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34093 Fatih, Istanbul, Türkiye
,
Ayşe Merve Şenol
d   Program of Medical Laboratory Techniques, Department of Medical Services and Techniques, University of Health Sciences, Üsküdar, 34668, Istanbul, Türkiye
,
Pelin Tokalı
e   Department of Veterinary Physiology, Faculty of Veterinary Medicine, Kafkas University, 36100, Kars, Türkiye
,
Halil Şenol  ∗
c   Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34093 Fatih, Istanbul, Türkiye
,
Feyzi Sinan Tokalı∗
f   Kafkas University, Kars Vocational School, Department of Material and Material Processing Technologies, 36100 Kars, Türkiye
,
Fahri Akbaş
b   Bezmialem Vakif University, Faculty of Medicine, Department of Medical Biology, 34093 Fatih, Istanbul, Türkiye
,
Erbay Kalay
f   Kafkas University, Kars Vocational School, Department of Material and Material Processing Technologies, 36100 Kars, Türkiye
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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.

Key words

Mannich base - rhodanine - thiazolidine-2,4-dione - molecular docking - A549

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.
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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
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