Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity.

ABSTRACT: Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for 18 polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 cells and calculated free energies of binding following docking the compounds into models of alphabeta-tubulin. These docking calculations coupled with HINT interaction analyses are able to represent the complex structures and the binding modes of inhibitors such that calculated and measured free energies of binding correlate with an r(2) of 0.76. Structural analysis of the binding pocket identifies important intermolecular contacts that mediate binding. As seen experimentally,

SUBMITTER: Tripathi A 

PROVIDER: S-EPMC2362145 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature