A greener approach toward N − 1 heteroarylation of indoles: Synthesis and in vitro evaluation of potential anti-proliferative agents

Abstract

In view of known antitumor and cytotoxic properties of 2- and 3-pyridinyl substituted indole derivatives, respectively a number of isomeric N-pyridinyl substituted indoles and their analogs were synthesized as potential cytotoxic agents. A greener approach was developed to synthesize these compounds via an ultrasound assisted selective N − 1 heteroarylation of indoles. The methodology involved reaction of indoles with heteroaryl halides in PEG-400 under ultrasound irradiation. One of the products i.e. 1-(pyrimidin-2-yl)-1H-indole was further functionalized via Pd-mediated CH activation at C-2 on the indole ring. All the synthesized N − 1 heteroarylindoles were tested for their in vitro anti-proliferative properties against cancer (leukemia) and non-cancerous cell lines. Some of the compounds showed promising and selective cytotoxic effects toward leukemia cells. Keywords: Indole, Heteroarylation, Ultrasound, Cytotoxicity