Design, synthesis and in vitro cytotoxicity studies of novel β-carbolinium bromides

Bioorg Med Chem Lett. 2017 Mar 15;27(6):1379-1384. doi: 10.1016/j.bmcl.2017.02.010.

P O Venkataramana Reddy ¹, Shriprada Mishra ¹, Mukund P Tantak ¹, Kumar Nikhil ², Rachna Sadana ³, Kavita Shah ⁴, Dalip Kumar ⁵

Affiliations

1 Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
2 Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States.
3 Department of Natural Sciences, University of Houston - Downtown, Houston, TX 77002, United States.
4 Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. Electronic address: shah23@purdue.edu.
5 Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.

PMID: 28254167 DOI: 10.1016/j.bmcl.2017.02.010

Abstract

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 IC₅₀ values of <10μM against tested Cancer cell lines. The most potent analogue 16l was broadly active against all the tested Cancer cell lines (IC₅₀=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.

Keywords

Apoptosis; In vitro cytotoxicity; Microwave; β-Carbolinium bromides.

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