Anti-tumor activity of novel biisoquinoline derivatives against breast cancers

作者：Jaiswal Aruna S; Hirsch Weil Dimitri; Proulx Erick R; Hong Sukwon^*; Narayan Satya

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(20): 4850-4853.

DOI：10.1016/j.bmcl.2014.08.053

• Breast cancer
• Biisoquinoline
• Noscapine
• MCF7
• MDA-MB231

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).

• 出版日期2014-10-15