Development of novel 1,2,4-triazole containing compounds with anticancer and potent anti-CB1 activity

Yıldırım S., Ayvaz A., Mermer A., Kocabaş F.

Journal of Biomolecular Structure and Dynamics, vol.42, no.8, pp.3862-3873, 2024 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 42 Issue: 8
  • Publication Date: 2024
  • Doi Number: 10.1080/07391102.2023.2239909
  • Journal Name: Journal of Biomolecular Structure and Dynamics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core
  • Page Numbers: pp.3862-3873
  • Keywords: 1,2,4-Triazole, anti-cancer, green metrics, microwave irradiation, molecular docking, ultrasonication
  • Karadeniz Technical University Affiliated: Yes


There is still an unmet need for novel and improved anti-cancer compounds. Nitrogen atoms have heterocyclic ring moieties, which have been shown to have powerful anticancer properties in both natural and synthetic derivatives. Due to their dipole character, hydrogen bonding capacity, rigidity and solubility, 1,2,4-triazoles are particularly effective pharmacophores, interacting with biological receptors with high affinity. Thus, novel 1,2,4-triazole-containing molecular derivatives were synthesized using green chemistry methods, microwave irradiation and ultrasonication, and these methods’ operational simplicity and maximum greener synthetic efficiency with green chemistry metrics calculations will be attractive for academic and industrial research and tested against three distinct human cancer cell lines including PANC1 (pancreatic cancer), DU145 (prostate cancer), MCF7 (breast cancer) and one fibroblast cell line (HDF). Here, we showed that compounds 5e and 5f were similar to CB1 antagonists in structure, binding affinity and poses. In addition, compounds 5e–g decreased the viability of pancreatic and prostate cancer cells, albeit with cytotoxicity to HDF cells. The IC50 values for PANC1 cells were between 5.9 and 7.3 µM for compounds 5e–g. Cell cycle analysis showed that the effect of compounds 5e–g in cancer cell growth was largely due to cell cycle arrest at S-phase. In sum, novel 1,2,4-triazole-containing compounds with anticancer and potent anti-CB1 activity have been developed. Communicated by Ramaswamy H. Sarma.