Synthesis, Characterization and <i>In Vitro</i> and <i>In Silico</i> Biological Evaluation of New Mannich-Based Rhodanine and Thiazolidine-2,4-dione Derivatives as Potential Anti-Lung-Cancer Agents

ATEŞOĞLU Ş., ÇAKIR F., Senol A. M., Tokali P., ŞENOL H., Tokali F. S., ...Daha Fazla

SYNLETT, cilt.36, sa.17, ss.2939-2947, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 17
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1055/a-2541-1072
  • Dergi Adı: SYNLETT
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica
  • Sayfa Sayıları: ss.2939-2947
  • Anahtar Kelimeler: A549, Mannich base, molecular docking, rhodanine, thiazolidine-2,4-dione
  • Bezmiâlem Vakıf Üniversitesi Adresli: Evet

Özet

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 mu M 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.