New 1H-1,2,3-triazole analogues of boswellic acid are potential anti-breast cancer agents

Official URL: https://dx.doi.org/10.1016/j.molstruc.2024.139447

In this work, we describe the synthesis of 12 new pentacyclic triterpene amides (3a-3l) and 11 new 1H-1,2,3-triazole analogues (5a-5k) of 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA) and evaluated them for their human breast cancer (MDA-MB-231) growth inhibitory activities. The resulting compounds were characterized by 1H NMR, 13C NMR, and HR-ESI-MS spectroscopy. X-ray crystallography unambiguously confirmed the exact structure of compound 3a. The cytotoxic potential of the synthesized compounds was scrutinized against triple-negative breast cancer (MDA-MB-231) and normal (MCF-10A) cell lines. Furthermore, all the synthesized derivatives exhibited significant anti-proliferative activities with IC50 values ranging from 8.1 ± 0.2 to 18.5 ± 0.4 μM. Among them, compounds 5a and 5i exhibited noteworthy activities and were several times more potent than the parent compound β-AKBA. Furthermore, molecular docking analysis predicted that these molecules exhibit their anti-proliferative effects by binding to the folate receptor alpha (FRα). Overall, this new study may pave the way to medicinal analogues of β-AKBA as anti-breast cancer agents.