Chemical Biology Laboratory, Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
Eur J Med Chem. 2010 Jun;45(6):2173-81. doi: 10.1016/j.ejmech.2010.01.054. Epub 2010 Feb 2.
New phenanthrylphenol-pyrrolobenzodiazepine (PP-PBD) conjugates have been synthesized and evaluated for their biological activity. One of the compounds 4a has been evaluated for its antiproliferative activity on 57 human tumour cell lines. The growth inhibition of 4a-c has been determined by MTT viability assay on MCF-7 cell line. Among them, 4c showed most potent growth inhibition. Based on this, an attempt was made to rationalize their mechanism of action through cell cycle analysis and DNA interaction studies. The effect of the lead compound 4c on MCF-7 cell growth associated with cell cycle arrest in G1 phase, followed by apoptosis. Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation.
新的菲咯啉-吡咯并苯二氮杂卓（PP-PBD）缀合物已被合成并评估其生物活性。其中一种化合物 4a 已在 MCF-7 细胞系上评估其对 57 个人类肿瘤细胞系的抗增殖活性。通过 MTT 活力测定法测定 4a-c 的生长抑制率。其中，化合物 4c 表现出最强的生长抑制作用。基于此，通过细胞周期分析和 DNA 相互作用研究，试图合理推断其作用机制。先导化合物 4c 对 MCF-7 细胞生长的影响与 G1 期细胞周期阻滞有关，随后是细胞凋亡。我们的研究结果表明，菲咯啉-吡咯并苯二氮杂卓缀合物 4c 是一种细胞周期蛋白 D1 抑制剂，可被视为一种有前途的针对乳腺癌的先导化合物，值得进一步研究。
