Optically pure chiral copper(II) complexes of rosin derivative as attractive anticancer agents with potential anti-metastatic and anti-angiogenic activities

Abstract

The development of optically pure drugs is the trend of new drugs research. Searching for optically pure metallodrugs against cancer has not been taken seriously. [CuL4Cl]Cl·2CH2Cl2·H2O (1) and [CuL4Br]Br·2CH2Cl2 (2) (L = 2-amino-5-dehydroabietyl-1,3,4-thiadiazole), two rosin-derivative based optically pure chiral copper(II) complexes, are rationally synthesized as potential anticancer agents. 1 exhibits effective in vitro and in vivo anticancer activities and tolerable toxicities. 1 promotes MCF-7 cell death by combination of cell arrest at G1 phase, apoptosis (both extrinsic and intrinsic apoptotic pathways), anti-metastasis, anti-angiogenesis, damage of DNA, protein and lipid, and autophagy mediated by the oxidative stress which is confirmed by ROS generation and intracellular glutathione depletion assays. 1 can be identified as a lead anticancer molecule of therapeutic importance. This work may offer insights into the design and mechanism study of multifunctional optically pure metal-based anticancer candidates derived from natural products.