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, vol.1358, 2026 (SCI-Expanded, Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 1358
  • Publication Date: 2026
  • Doi Number: 10.1016/j.molstruc.2026.145286
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Keywords: 1,2-dithiole, Anticancer activity, Drug-likeness, Fukui function, X-ray analysis
  • Istanbul Gelisim University Affiliated: Yes

Abstract

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.