Design, synthesis and biological evaluation of Novel 6-azophenylcoumarin-3-formamido derivatives and a copper (II) complex

Abstract

The azobenzene coumarin derivatives 2–10, in which the coumarin moiety is linked to substituted phenyl and pyridine groups via amide bonds, and a copper complex with compound 8 (8-CuCl2) were designed and synthesized, and their anticancer activities were investigated. Compounds 2–10 and 8-CuCl2 exhibited different degrees of anticancer activities against four cancer cell lines (HeLa, A549, MCF-7, and HepG-2). Among them, compound 6 exhibited stronger cytotoxicity (IC50 = 0.51 ± 0.22 μM) against A549 cell lines and was less toxic to normal cells than Doxorubicin (DOX) (IC50 = 1.18 ± 0.03 μM). Compound 8 exhibited stronger cytotoxicity against MCF-7 cell lines than DOX with an IC50 value 48 times higher than DOX (IC50 = 0.42 ± 0.23 μM for 8; IC50 = 20.64 ± 3.67 μM for DOX). Meanwhile, compound 8 was much less toxic to normal human umbilical vein endothelial cells (HUVEC) cells than DOX with a 3000 times higher selectivity index (SI) (SI > 238.10 for 8; SI = 0.078 for DOX). The results of cell apoptosis and cycle assays showed that compound 6 induced apoptosis in A549 cells more considerably and blocked cells in the S phase, whereas compound 8 induced late apoptosis in MCF-7 cells and blocked cells in the S phase. Ultraviolet and fluorescence spectroscopy analyses revealed that compounds 6 and 8 bound to deoxyribonucleic acid (DNA) via intercalation. In summary, compound 8 was developed as a potential and effective cytotoxicity against MCF-7 cell lines worthy of further investigation.