Isatin 1,2,3-triazoles as potent inhibitors against caspase-3

Sixteen disubstituted 1,2,3-triazoles were prepared using the Huisgen cycloaddition reaction and evaluated as inhibitors against caspase-3. The two most potent inhibitors were found to be (S)-1-((1-(2,3-dihydrobenzo[ b][ 1,4] dioxin-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-((2-(methoxymethyl) pyrrolidin-1-yl)sulfonyl) indoline-2,3-dione (7f) and (S)-1-((1-benzyl-1H-1,2,3-triazol-5-yl)methyl)-5-((2-(methoxymethyl) pyrrolidin-1-yl) sulfonyl) indoline-2,3-dione (8g) with IC(50)-values of 17 and 9 nM, respectively. Lineweaver-Burk plots revealed that these two triazoles show competitive inhibitory mechanism against caspase-3. (C) 2011 Elsevier Ltd. All rights reserved.