Toward the Identification of Novel Carbonic Anhydrase XIV Inhibitors using 3D-QSAR Pharmacophore Model, Virtual Screening and Molecular Docking Study
Tao Liu, Lu Zhou, Taijin Wang, Lufen He and Xiangyang TangAffiliation:
College of Chemical Engineering, Sichuan University, Sichauan, Chengdu, 610065, China.
AbstractCarbonic anhydrases XIV (CA XIV) is responsible for health issue and a therapeutic target of many disorders like epilepsy, and retinopathy. Here we described the first pharmacophore model for human CA XIV to identify the new scaffolds compounds. Hypotheses 1, with the highest cost difference, best correlation coefficient as well as the lowest RMSD, was validated by test set and Fischer method. Then, Hypotheses 1 was used for virtual screening in 718361 databases compounds. After Lipinski’s rule of five and ADMET properties, 148 compounds with high potential activity were filtered and estimated by docking. Finally, 6 new scaffold compounds turned out to be potential as new class CA XIV antagonists. In addition, we also analyzed the interaction between compound 7 and ten CA isoforms and explained various inhibitions caused by their distinct residues. Therefore, this paper could be helpful in novel CA XIV inhibitors discovery and its selective inhibitors design.
Carbonic anhydrase XIV, Molecular docking, Pharmacophore model, Selective inhibitor, Virtual screening, 3DQSAR.
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