Synthesis, crystal structure and Hirshfeld surface analyses, crystal voids, interaction energy calculations and energy frameworks and biological studies of oxime barbiturate derivatives

Kıncal S., Topkaya C., HÖKELEK T., Çetin E. S., Güp R.

Journal of Molecular Structure, vol.1302, 2024 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1302
  • Publication Date: 2024
  • Doi Number: 10.1016/j.molstruc.2023.137451
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Keywords: Barbituric acid, Crystal structure, Cytotoxicity, DNA interaction, Energy framework, Hirshfeld surface analysis, Hydrazone, Interaction energy, Oxime
  • Hacettepe University Affiliated: Yes


This study focuses on a newly synthesized compound using 5-acetyl-1,3-dimethyl-barbituric acid and p-chloroisonitrosophenylhydrazine, inspired by a previously synthesized and characterized oxime barbiturate derivative. The compound's biological activity is investigated in comparison to the previously illuminated compound. Additionally, a thorough examination of the The significance of H-atom contacts in determining crystal packing has been validated by Hirshfeld surface representations. Void analysis demonstrates the absence of significant voids, contributing to mechanical stability. Intermolecular interaction energies underscore the dominance of electrostatic and dispersion contributions. Energy frameworks visually convey the magnitude of interaction energies, emphasizing the nearly equal strength of electrostatic and dispersion contributions in crystal stabilization. Furthermore, the study examines the biological activities of the synthesized compounds on various cancer cell lines. Cytotoxicity analyses via MTT assays reveal substantial inhibitory effects of the compounds on cancer cells over 24, 48 and 72 h, displaying dose-dependent responses. Particularly, despite lower cytotoxicity compared to cisplatin, the compounds exhibit comparable activity to etoposide. Cytotoxic selectivity indices (SI) suggest potential selective cytotoxicity against cancer cells. In conclusion, this comprehensive analysis integrates crystallographic insights with biological activity assessments, providing a holistic understanding of the structural and functional properties of the synthesized compounds. The results contribute to advancements in crystal engineering and offer a promising avenue for the development of anticancer agents with selective cytotoxicity.