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

Yang Jiang; Trond Vidar Hansen

doi:10.1016/j.bmcl.2011.01.110

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

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1626-9. doi: 10.1016/j.bmcl.2011.01.110. Epub 2011 Jan 31.

Authors

Yang Jiang¹, Trond Vidar Hansen

Affiliation

¹ School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, Oslo, Norway. yang.jiang@farmasi.uio.no

PMID: 21324681
DOI: 10.1016/j.bmcl.2011.01.110

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Caspase Inhibitors*
Enzyme Inhibitors / pharmacology*
Isatin / chemistry*
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Caspase Inhibitors
Enzyme Inhibitors
Triazoles
Isatin