Synthesis and antiproliferative activity of Daidzein bridged bis-[1,2,3]-triazole derivatives: Double click strategy

Abstract

A series of unsymmetrical bis-[1,2,3]-triazole-daidzein hybrid derivatives have been synthesized from natural isoflavone, Diadzein through terminal alkyne tethered intermediate using double click strategy, Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition. All the synthesized derivatives were evaluated for their in vitro anti-proliferative activity against three human cancer cell lines A549 (lung), HeLa (cervical), and MDA-MB-231 (breast). Among the tested thirteen hybrid compounds, 5d, e, g, h, i, j, k, l and m derivatives showed potent anti-proliferative activity with GI 50 values range of 0.14 (>) 0.88 μM against all the three cancer cell lines, particularly compounds 5j and k showed significant activity against HeLa and MDA-MB-231 cell lines and compounds 5d, e and i showed selective potency against A549 cancer cell line. The test results revealed that the compound 5l has very close GI 50 value 0.14 μM as compared with positive control, Nocodazole reference, against breast cancer cell line (MDA-MB-231), it could be further optimized to develop promising future anticancer drug candidate.