Tubulin inhibitors: pharmacophore modeling, virtual screening and molecular docking.

ABSTRACT:

Aim

To construct a quantitative pharmacophore model of tubulin inhibitors and to discovery new leads with potent antitumor activities.

Methods

Ligand-based pharmacophore modeling was used to identify the chemical features responsible for inhibiting tubulin polymerization. A set of 26 training compounds was used to generate hypothetical pharmacophores using the HypoGen algorithm. The structures were further validated using the test set, Fischer randomization method, leave-one-out method and a decoy set, and the best model was chosen to screen the Specs database. Hit compounds were subjected to molecular docking study using a Molecular Operating Environment (MOE) software and to biological evaluation in vitro.

Results

Hypo1 was demonstrated to be the best pharmacophore

SUBMITTER: Niu MM 

PROVIDER: S-EPMC4088285 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature