Triazole‐tethered boswellic acid derivatives against breast cancer: Synthesis, in vitro, and in‐silico studies.

• Sixteen new analogues (3 – 8, 10a-j) of β-AKBA and β-ABA were synthesized. • The cytotoxic potential of the synthesized compounds was scrutinized against the triple-negative breast cancer (MDA-MB-231) and normal cell lines (MCF-10A). • Interestingly, all the synthesized derivatives exhibited highly potent anti-proliferative activity with IC 50 values in range of 4.45 to 14.45 µM. • Compounds 10f, 10i and 10j exhibited exceptional inhibitory potency and found several times more potent than the parent compounds 1 and 2. • The compounds 5 and 6 were sustained by X-ray crystallography, while molecular docking of the active compounds was also performed A series of new analogues of 3- O -acetyl-11-keto- β -boswellic acid (β -AKBA, 1), 3- O -acetyl- β -boswellic acid (β -ABA, 2) (3–8) and 1 H -1,2,3-triazole hybrids of β -AKBA (10a-j) were synthesized by employing highly efficient "Click" chemistry reaction protocol. All synthesized compounds were characterized by 1H-, 13C NMR, and HRMS spectroscopy. The structures of compounds 5 and 6 were unambiguously confirmed by the single crystal X-ray analysis diffraction method. The cytotoxic potential of the synthesized compounds was scrutinized against the triple-negative breast cancer (MDA-MB-231) and normal (MCF-10A) cell lines. Furthermore, all the synthesized derivatives exhibited highly potent anti-proliferative activity with IC 50 values ranging from 4.45 to 14.45 µM. Among them, compounds 10j, 10f, and 10i exhibited exceptional inhibitory potency and were found several times more potent than the parent compounds 1 and 2. Additionally, the cheminformatics method was used to identify the potential drug target of the most potent compounds (10j, 10f, and 10i) and their binding mechanism with the selected drug target was predicted through molecular docking. The combined 2D-similarity searching, and structure-based binding investigation predict that these compounds can target CHK1 to produce anti-cancer effects in TNBC. This study lays a good foundation for new triterpenic triazole analogues of boswellic acids and could be effective anticancer leads in breast cancer therapeutics. [ABSTRACT FROM AUTHOR]