Medicinal and Process Chemistry Division, Central Drug Research Institute, CDRI-CSIR, Lucknow, India.
Bioorg Med Chem Lett. 2010 Dec 1;20(23):7127-31. doi: 10.1016/j.bmcl.2010.09.040. Epub 2010 Sep 21.
A small library of novel benzocoumarin derivatives based on naturally occurring neo-tanshinlactone scaffold was constructed and their antiproliferative activities against breast cancer cells MCF-7 and MDA-MB-231 were evaluated. A number of derivatives showed good anti-breast cancer activity, in some cases higher to that of the reference compound tamoxifen. In particular, benzocoumarins Bc-5, Bc-8 and Bc-9 strongly inhibited the proliferation of MCF-7 cancer cell line with the IC(50) values of 3.8, 7.9 and 6.5 μM, respectively. The compounds were capable of inducing nuclear fragmentation, cell cycle arrest and caspase dependent apoptosis in MCF-7 cell lines. In addition, these derivatives were devoid of cytotoxic effect against normal osteoblast cells. These synthetic benzocoumarins hold promises for developing safer alternative to the existing anti-breast cancer agents.
构建了一个基于天然 neo-tanshinlactone 骨架的新型苯并香豆素衍生物小文库，并评估了它们对乳腺癌细胞 MCF-7 和 MDA-MB-231 的增殖抑制活性。许多衍生物表现出良好的抗乳腺癌活性，在某些情况下比参考化合物他莫昔芬更高。特别是苯并香豆素 Bc-5、Bc-8 和 Bc-9 强烈抑制 MCF-7 癌细胞系的增殖，其 IC50 值分别为 3.8、7.9 和 6.5 μM。这些化合物能够诱导 MCF-7 细胞系中的核碎裂、细胞周期停滞和 caspase 依赖性细胞凋亡。此外，这些衍生物对正常成骨细胞没有细胞毒性作用。这些合成的苯并香豆素有望开发出更安全的替代现有抗乳腺癌药物的方法。
