Indolinones as Promising Scaffold as Kinase Inhibitors: A Review

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.

Synthesis and preliminary evaluation of 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones as angiogenesis inhibitors

“…Indeed, the structurally simpler indolin-2-one predecessor semaxanib (SU5416) 2 underwent a Phase III clinical trial for advanced colorectal cancer. 6 In recent work, we…”

Crystal structure of (Z)-methyl N'-(5,7-dibromo-1-(2-morpholinoethyl)-2- oxoindolin-3-ylidene)hydrazinecarbodithioate, C16H18Br2N4O2S2

“…1H-indole-2,3-dione derivatives possess av ariety of biological activities, including antitumor activity [2].I ntroduction of substituents at the 3-and 5-positions of the indolin-2-one ring have recently led to many derivatives possessing more potent antiumor activities [3,4].Inaddition, the introduction of an alkyl group or aryl group at the Natom of indolin-2-ones enhanced their cytotoxicity againstavarietyofcancercelllines [5,6]. Herein, we report thecrystal structure of oneofthe derivateswhich maybea potential anticancer agent.…”

Crystal structure of 1-(4-bromo-2-(2-morpholinoethylamino)phenyl)-2- morpholinoethane-1,2-dione, C18H24BrN3O4

“…1H-indole-2,3-dione derivatives have driven much attention for their bioactivities on anti-HIV [1], anticonvulsant[ 2] and antitumor activities [3,4].Ithas been reported that the introduction of substituents at the Natom of indolin-2-ones enhances their cytotoxicity against avariety of cancer cell lines [5,6]. In an attemptt oo btain compounds that might also exhibit antitumor properties, we carried out the reaction of 6-bromo-1-(2-bromoethyl)indoline-2,3-dione with an excess of morpholine.…”