Anti-tumor activity of novel biisoquinoline derivatives against breast cancers

Breast cancer is classified into three groups according to its expression of hormone/growth factor receptors: (i) estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). A series of methoxy- substituted biisoquinoline compounds have been synthesized as a potential chemotherapeutic agent for the triple-negative breast cancers which are especially challenging to manage. Structure activity relationship study revealed that rigid 6,60-dimethoxy biisoquinoline imidazolium compound (1c, DH20931) exhibited the significant growth inhibitory effects on both triple-positive and triple-negative human breast cancer cell lines with IC50 in the range of 0.3-3.9 mu M. The 1c (DH20931) is more potent than structurally related noscapine for growth inhibition of MCF7 cell line (IC50 = 1.3 vs 57 mu M) and MDA-MB231 cell line (IC50 = 3.9 vs 64 mu M). (C) 2014 Elsevier Ltd. All rights reserved.