Triazole‐tethered boswellic acid derivatives against breast cancer: Synthesis, in vitro, and in‐silico studies
Satya Kumar Avula, Najeeb Ur Rehman, Faizullah Khan, Obaid Ullah, Sobia Ahsan Halim, Ajmal Khan, Muhammad U. Anwar, Shaikh Mizanoor Rahman, René Csük, Ahmed Al-Harrasi
Abstract
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 1 H-, 13 C 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.