Indolinones as Promising Scaffold as Kinase Inhibitors: A Review

C.      R. Prakash; S.      Raja

doi:10.2174/138955712798995039

Abstract

Kinases are probably the most important signaling enzymes, which represent about 20% of the druggable genome. Currently, more than 150 kinases are known. So, kinase inhibition therapy has become a very important area of drug research since most of our diseases are related to intra or intercellular signaling by kinases. Indole alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, antitumor. Among this chemical family, indolinone displays very promising antitumor properties by inhibiting various kinase families. These small molecules have a low molecular weight and most of them bind to protein kinases competing with ATP for the ATP-binding site. This review focuses on the indolinone based drugs approved for the treatment of cancer, drugs under clinical trial and then chemical diversity of various synthetic analogues of indolinone and their metabolites as various kinase inhibitors. This review also focused on structural activity relationship (SAR), mechanisms of action and biological targets through which indolinone and its derivatives display their antitumor activity.

Keywords: Anticancer, growth factor, indole, inhibitor, isatin, Kinase, antitumor, immunodeficiency, phosphorylation, endothelial, ploidy, Angiogenesis, TrkA Inhibitor