Molecular modeling study, synthesis and biological evaluation of combretastatin A-4 analogues as anticancer agents and tubulin inhibitors.

ABSTRACT: As the major structural component of microtubules, tubulin is an interesting target for the development of anticancer agents. In this study, 64 tubulin polymerization inhibitors of five-membered heterocycle-based combretastatin A-4 analogues were studied by a combination of molecular modeling techniques including 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation. The CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) models were established with desirable statistical parameters and excellent predictive ability. 20 ns MD simulations were successfully performed to confirm the detailed binding mode and validate the rationality of docking results. Combining the binding free energy calculations and 3D-QSAR results, some n

SUBMITTER: Quan YP 

PROVIDER: S-EPMC6083788 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature