A convenient synthesis of ethyl 5-amino-3-thioxo-3H-1,2-dithiole-4-carboxylate: Crystal structure, computational studies, anticancer activity, and drug-likeness evaluation

ELHATY I. A. M., Kheder N. A., Muhsinah A. B., Mabkhot Y. N.

Journal of Molecular Structure, cilt.1358, 2026 (SCI-Expanded, Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1358
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.molstruc.2026.145286
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: 1,2-dithiole, Anticancer activity, Drug-likeness, Fukui function, X-ray analysis
  • İstanbul Gelişim Üniversitesi Adresli: Evet

Özet

The reaction of ethyl cyanoacetate with CS2 in a DMF/K2CO3 mixture unexpectedly afforded the title compound. Chemical structure of this compound was confirmed using spectral and X-ray analysis. Hirshfeld surface analysis, HOMO–LUMO orbital energies, MEP surface mapping, Mulliken charge distribution, and Fukui function were employed to analyze its structure. Further, the biological activity, in silico predictions of toxicity, and drug-likeness were studied. Compound 3 showed a wide HOMO-LUMO gap (7.742 eV) and potent cytotoxicity, with IC50 values of 2.6 ± 0.3 µg/mL (MCF-7), 21.8 ± 1.6 µg/mL (HepG-2), and 20.8 ± 0.6 µg/mL (HCT-116). Hirshfeld surface and fingerprint analyses confirmed the dominance of S∙∙∙H, H∙∙∙H, C∙∙∙H, and O∙∙∙H interactions in stabilizing its crystal lattice. For the synthesized compound, OSIRIS predicted no mutagenicity, tumorigenicity, or reproductive toxicity and also indicated better solubility and a higher drug-score. Overall, the electronic characteristics align with biological function, highlighting it as a promising antitumor candidate.