Click chemistry-assisted synthesis of novel aminonaphthoquinone-1,2,3-triazole hybrids and investigation of their cytotoxicity and cancer cell cycle alterations

A series of 12 novel 1,4-naphthoquinone-1,2,3-triazole hybrids were designed and synthesized through copper-catalyzed click reaction of 2-(prop-2-ynylamino)naphthalene-1,4-dione (3) and different azidomethyl-benzene derivatives. The synthesized compounds were assessed for their anticancer activity against three cancer cell lines (MCF-7, HT-29 and MOLT-4) by MTT assay. The results showed that the majority of the synthesized compounds displayed cytotoxic activity. Derivatives 6f and 6h, bearing 4-trifluoromethyl-benzyl and 4-tert-butyl-benzyl groups, respectively, as well as intermediate 3 demonstrated good cytotoxic potential against all tested cancer cell lines, among which compound 6f showed the highest activity. Flow cytometric analysis revealed that compounds 3, 6f and 6h arrested cell cycle at G0/G1 phase in MCF-7 cells. Therefore, synthesized aminonaphthoquinone-1,2,3-triazole derivatives can be introduced as promising molecules for further development as potential anticancer agents.