Venkataramana Reddy P O, Mishra Shriprada, Tantak Mukund P, Nikhil Kumar, Sadana Rachna, Shah Kavita, Kumar Dalip
Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States.
Bioorg Med Chem Lett. 2017 Mar 15;27(6):1379-1384. doi: 10.1016/j.bmcl.2017.02.010. Epub 2017 Feb 9.
A series of novel β-carbolinium bromides has been synthesized from easily accessible β-carbolines and 1-aryl-2-bromoethanones. The newly synthesized compounds were evaluated for their in vitro anticancer activity. Among the synthesized derivatives, compounds 16l, 16o and 16s exhibited potent anticancer activity with IC values of <10μM against tested cancer cell lines. The most potent analogue 16l was broadly active against all the tested cancer cell lines (IC=3.16-7.93μM). In order to test the mechanism of cell death, we exposed castration resistant prostate cancer cell line (C4-2) to compounds 16l and 16s, which resulted in increased levels of cleaved PARP1 and AO/EB staining, indicating that β-carbolinium salts induce apoptosis in these cells. Additionally, the most potent β-carbolines 16l and 16s were found to inhibit tubulin polymerization.
一系列新型β-咔啉溴化物已由易于获得的β-咔啉和1-芳基-2-溴乙酮合成。对新合成的化合物进行了体外抗癌活性评估。在合成的衍生物中，化合物16l、16o和16s表现出强效抗癌活性，对测试的癌细胞系的IC值<10μM。最有效的类似物16l对所有测试的癌细胞系都具有广泛的活性（IC=3.16-7.93μM）。为了测试细胞死亡机制，我们将去势抵抗性前列腺癌细胞系（C4-2）暴露于化合物16l和16s，这导致裂解的PARP1水平升高和AO/EB染色增加，表明β-咔啉盐在这些细胞中诱导凋亡。此外，发现最有效的β-咔啉16l和16s可抑制微管蛋白聚合。
