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  • Title: Anti-tumor activity of novel biisoquinoline derivatives against breast cancers.
    Author: Jaiswal AS, Hirsch-Weil D, Proulx ER, Hong S, Narayan S.
    Journal: Bioorg Med Chem Lett; 2014 Oct 15; 24(20):4850-3. PubMed ID: 25240616.
    Abstract:
    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 6,6'-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 μM. The 1c (DH20931) is more potent than structurally related noscapine for growth inhibition of MCF7 cell line (IC50=1.3 vs 57 μM) and MDA-MB231 cell line (IC50=3.9 vs 64 μM).
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