title: Design, synthesis and in vitro cytotoxicity studies of novel β-carbolinium bromides.
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 IC50values 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.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
authors.forename: P O
authors.initials: PO
authors.lastname: Venkataramana Reddy
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
authors.forename: Shriprada
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.
authors.forename: Mukund P
authors.initials: MP
authors.lastname: Tantak
authors.affiliation: Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: Kumar
authors.initials: K
authors.lastname: Nikhil
authors.affiliation: Department of Natural Sciences, University of Houston - Downtown, Houston, TX 77002, United States.
authors.forename: Rachna
authors.initials: R
authors.lastname: Sadana
authors.affiliation: Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. Electronic address: shah23@purdue.edu.
authors.forename: Kavita
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.
authors.forename: Dalip
authors.initials: D
authors.lastname: Kumar
mesh_terms: D001965:Bromides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology
chemical_list: D001965:Bromides; D002243:Carbolines
keywords: Apoptosis; In vitro cytotoxicity; Microwave; β-Carbolinium bromides