新型双异喹啉衍生物对乳腺癌的抗肿瘤活性
Anti-tumor activity of novel biisoquinoline derivatives against breast cancers.
作者信息
Jaiswal Aruna S, Hirsch-Weil Dimitri, Proulx Erick R, Hong Sukwon, Narayan Satya
机构信息
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA.
Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
出版信息
Bioorg Med Chem Lett. 2014 Oct 15;24(20):4850-3. doi: 10.1016/j.bmcl.2014.08.053. Epub 2014 Sep 2.
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).
乳腺癌根据其激素/生长因子受体的表达分为三组：（i）雌激素受体（ER）和孕激素受体（PR）阳性；（ii）人表皮生长因子受体2（HER2）阳性；以及（iii）ER、PR和HER2阴性（三阴性）。一系列甲氧基取代的双异喹啉化合物已被合成，作为治疗三阴性乳腺癌的潜在化疗药物，这类癌症的治疗尤其具有挑战性。构效关系研究表明，刚性的6,6'-二甲氧基双异喹啉咪唑鎓化合物（1c，DH20931）对三阳性和三阴性人乳腺癌细胞系均表现出显著的生长抑制作用，IC50范围为0.3 - 3.9 μM。在MCF7细胞系（IC50 = 1.3对57 μM）和MDA - MB231细胞系（IC50 = 3.9对64 μM）的生长抑制方面，1c（DH20931）比结构相关的那可丁更有效。
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