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

Abstract

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

Keywords:

• 1,2,4-Triazole
• microwave irradiation
• ultrasonication
• molecular docking
• anti-cancer
• green metrics

Author contributions

AA and AM designed and synthesized the compounds. AA performed all characterization methods for synthesized compounds. SY planned the experiments, collected the data and wrote the manuscript. AM and FK designed the studies and wrote the manuscript.

Disclosure statement

All authors declare that there is no conflict of interest.

Data availability statement

The data that supports the findings of this study are available in the supporting information of this article.

Additional information

Funding

This study was supported by TUBITAK (Project no. 217Z085).