Structure-Based Pharmacophore Design and Virtual Screening for Novel Tubulin Inhibitors with Potential Anticancer Activity.

ABSTRACT: Tubulin inhibitors have been considered as potential drugs for cancer therapy. However, their drug resistance and serious side-effects are the main reasons for clinical treatment failure. Therefore, there is still an urgent need to develop effective therapeutic drugs. Herein, a structure-based pharmacophore model was developed based on the co-crystallized structures of the tubulin with a high resolution. The model including one hydrogen-bond acceptor feature, two aromatic features, and one hydrophobic feature was further validated using the Gunner-Henry score method. Virtual screening was performed by an integrated protocol that combines drug-likeness analysis, pharmacophore mapping, and molecular docking approaches. Finally, five hits were selected for biological evaluation. The results i

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC6749218 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature