Chemoselective synthesis, structural elucidation, antitumor activity, Hirshfeld surface, and Fukui functions analysis of new thiophene derivatives

Bin Muhsinah A., Kheder N. A., Soliman S. M., Ghabbour H. A., ELHATY I. A. M., Mahmoud N. S., ...More

Journal of Molecular Structure, vol.1343, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1343
  • Publication Date: 2025
  • Doi Number: 10.1016/j.molstruc.2025.142826
  • 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: Anticancer activity, Chemoselective synthesis, Fukui function, Hirshfeld surface analysis, Thieno[3,2-c]pyrazole, Thiophene
  • Istanbul Gelisim University Affiliated: Yes

Abstract

Thiophene derivatives are well known for their unique biological activities. This study describes convenient synthetic approaches to new thiophene derivatives 6 and 12. Their chemical structures were investigated using different Spectroscopic analysis techniques. In addition, the 3D structure of thiophene 6 is explored using single-crystal X-ray analysis. The molecular structure of thiophene 6 was crystallized in the monoclinic P21/c. The asymmetric unit comprises a single independent molecule, emphasizing the compound's structural simplicity and symmetry. Hirshfeld analysis of 6 was performed where the molecular packing is dominated by H…H and O…H contacts. The percentages of the H…H and O…H contacts are 47.7 and 25.8%, respectively. Fukui analysis indicated that atoms C1, C7, and H38 in thiophene 6, and S8, C6, and C7 in thiophene 12 were identified as the most susceptible to nucleophilic attack. Electrophilic reactivity was highest at O21, O20, and S13 in thiophene 6, and at O12, N2, and S13 in thiophene 12, highlighting the influence of heteroatoms on local reactivity. The newly synthesized thiophenes were evaluated in vitro to determine their efficacy against MCF-7, HepG2, and HCT-116 cell lines using the sulforhodamine B (SRB) assay. The results showed that compound 12 possesses more potent anticancer activity than 6.