Synthesis and Anticancer Activity Studies of Some Novel Indole Related Heterocycles

Abstract

Cancer is one of the prominent causes of death worldwide after heart disease. Identification of potent and selective anticancer drugs with reduced side effects is a serious concern to medicinal chemists. The thesis deals with the design, synthesis and anticancer activity studies of some newlineindole-related heterocycles. The thesis is divided into six chapters. The first chapter briefly highlights the synthesis and chemical properties of indole related heterocycles such as carbazole and and#946;-carboline derivatives. In addition, this chapter includes description about the importance of natural and synthetic carbazole and and#946;-carboline based anticancer agents. newlineThe second chapter is subdivided into two parts dealing with design, synthesis and anticancer activity studies of two different series of novel and#946;-carbolinium bromides. Part A of the chapter reports microwave-assisted rapid and high yielding synthesis of phenacyl-and#946;-carbolinium bromides by N2-quaternization of and#946;-carbolines with 1-aryl-2-bromoethanones in ethanol. The newlinemost potent and#946;-carbolinium bromides were found to display broad spectrum of anticancer activity against all the tested cancer cell lines (IC50 = 3.16-7.93 and#956;M) via apoptosis inducing pathway. Part B of the chapter describes the synthesis and anticancer activity studies of and#946;-carboline-1- newlinechalcones and their bromide salts which led to identify a potent compound with an IC50 value lower than 22.5 and#956;M against all the tested cancer cell lines. Further, preliminary mechanism of action studies indicated that chalcone tethered and#946;-carbolinium bromides triggered apoptosis in newlineMDA-MB-231cells. The third chapter illustrates a significant exploration of molecular iodine and triphenylphosphine combination enabled the facile construction of natural and#946;-carboline skeletons. newlineThe desired products were prepared from easily available indoles and tryptamines by in-situ cyclization of bis(indolyl)ketoamides involving the use of molecular iodine and newlinetriphenylphosphine in DMSO. The present strategy provides an attractive approach to access newline