Synthesis of arylidene-substituted gelastatin analogues and their screening for MMP-2 inhibitory activity

Abstract

A series of arylidene-substituted gelastatin analogues were synthesized in a divergent manner. Each analogue was obtained as a mixture of isomers. Calculation methods were devised to deduce the MMP-2 inhibitory activity of each isomer from the activity of an isomeric mixture and its composition. This protocol is suitable for rapidly generating a variety of arylidene-substituted gelastatin analogues and screening them for highly active inhibitors. © 2005 Elsevier Ltd. All rights reserved.