Novel 1,2,4-triazole-maleamic acid derivatives: synthesis and evaluation as anticancer agents with carbonic anhydrase inhibitory activity


Tapera M., Kekeçmuhammed H., TÜZÜN B., DURNA DAŞTAN S., Safa Çelik M., Taslimi P., ...More

Journal of Molecular Structure, vol.1313, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1313
  • Publication Date: 2024
  • Doi Number: 10.1016/j.molstruc.2024.138680
  • 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: Triazole, Hydrazole, Synthesis, Cytotoxic activity, Enzyme inhibition, Computational studies
  • Erciyes University Affiliated: Yes

Abstract

Hybrid compounds with 1,2,4-triazole ring and a hydrazone moiety were designed and synthesized by amine acylation of uncommon triaminogunidine derivatives using maleic anhydride. Synthesized compounds were characterized by various spectral techniques, including FTIR, 1H NMR, 13C NMR, and HRMS. Furthermore, the proposed structure of TM-2 was resolved by single-crystal X-ray analysis. The compounds were evaluated for their anticancer activity in vitro against the colon cancer cell line HCT116 and the ovarian cancer cell line A2780. Among them, some compounds, TM-3, TM-4, and TM-14, exhibited remarkable antiproliferative activity in the cell line A2780, with IC50 values of 6.11, 5.15, and 5.93 µM, respectively. Further investigation revealed that these compounds could inhibit cancerous cell growth by inducing an increase in caspase-3 activity. In addition, antioxidant capabilities, interaction with plasmid pBR322 DNA, and inhibitory effects against two physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms, namely hCA I and hCA II, of the synthesized compounds were also assessed. Finally, computational studies, such as DFT calculation, molecular docking, and in silico predictions of ADME/T analysis, were conducted to gain an understanding of the specific reactive sites of the compounds, the binding modes in the active sites, and the pharmacokinetic parameters of the newly synthesized hybrid compounds, which were calculated to establish their drug-likeness properties.