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; Furkan Çakır; Ayşe Merve Şenol; Pelin Tokalı; Halil Şenol; Feyzi Sinan Tokalı; Fahri Akbaş; Erbay Kalay

doi:10.1055/a-2541-1072

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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

^aBezmialem Vakif University, Institute of Health Sciences, Department of Biotechnology, 34093 Fatih, Istanbul, Türkiye

^bBezmialem Vakif University, Faculty of Medicine, Department of Medical Biology, 34093 Fatih, Istanbul, Türkiye

,

Furkan Çakır

^cBezmialem Vakif University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34093 Fatih, Istanbul, Türkiye

,

Ayşe Merve Şenol

^dProgram of Medical Laboratory Techniques, Department of Medical Services and Techniques, University of Health Sciences, Üsküdar, 34668, Istanbul, Türkiye

,

Pelin Tokalı

^eDepartment of Veterinary Physiology, Faculty of Veterinary Medicine, Kafkas University, 36100, Kars, Türkiye

,

Halil Şenol ∗

^cBezmialem Vakif University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34093 Fatih, Istanbul, Türkiye

,

Feyzi Sinan Tokalı∗

^fKafkas University, Kars Vocational School, Department of Material and Material Processing Technologies, 36100 Kars, Türkiye

,

Fahri Akbaş

^bBezmialem Vakif University, Faculty of Medicine, Department of Medical Biology, 34093 Fatih, Istanbul, Türkiye

,

Erbay Kalay

^fKafkas University, Kars Vocational School, Department of Material and Material Processing Technologies, 36100 Kars, Türkiye

› Author Affiliations

Abstract

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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

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References

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