Synthesis of fused 1,2,3-triazoles of Clioquinol via sequential CuAAC and C[sbnd]H arylation; in vitro anticancer activity, in silico DNA topoisomerase II inhibitory activity and ADMET

Abstract

Synthesis of some novel Clioquinol linked annulated 1,2,3-triazole hybrids (4a-4n) via step-economical copper-catalyzed cascade reactions was developed. It involves copper (I) catalyzed azide-alkyne cycloaddition (CuAAC) followed by intramolecular CH arylation of triazole ring in one pot. The structures of all the synthesized hybrids were confirmed by 1HNMR, 13CNMR, and Mass spectra. The in vitro anticancer screening against four human cancer cell lines including MCF-7, HeLa, A549, and PC33 revealed that the compounds 4c, 4h, 4j, and 4n exhibited good anticancer activities which are comparable to the standard drug etoposide. Molecular docking studies of potent compounds 4c, 4h, 4j, and 4n with DNA topoisomerase II revealed that they have a good affinity towards the target protein. In addition to this, in silico pharmacokinetic profile was achieved for the potent compounds 4c, 4h, 4j, and 4n using SWISS/ADME and pkCSM, and all the four compounds followed Lipinski, Ghose, Veber, Egan, and Muegge rules without any deviation.