Abstract
In the present paper 25 known thermolysin inhibitors were docked into thermolysin using the Internal Coordinate Mechanics (ICM™) software. Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout™ program. The docking studies indicated that all 25 inhibitors coordinated the catalytic zinc in bidentate or monodentate geometry. A ‘three-point’ pharmacophore model was proposed which consisted of a hydrophobic group, a negative ionizable group and a hydrogen bond acceptor group. Finally the pharmacophore model has been tested against a small compound library containing 18 highly, moderately, less active as well as inactive compounds. The screening indicated that the pharmacophore model could, identify highly active compounds in front of inactive or less active ones.
Keywords: Thermolysin inhibitors, molecular docking, pharmacophore models, antibacterial drugs, antihypertensive drugs, thermolysin, Listeeria, Clostridium, Staphyloccus, Pseudomonas, Vibrio
Mini-Reviews in Medicinal Chemistry
Title:Binding Modes and Pharmacophore Modelling of Thermolysin Inhibitors
Volume: 12 Issue: 6
Author(s): M. T.H. Khan, Y. Wuxiuer and I. Sylte
Affiliation:
Keywords: Thermolysin inhibitors, molecular docking, pharmacophore models, antibacterial drugs, antihypertensive drugs, thermolysin, Listeeria, Clostridium, Staphyloccus, Pseudomonas, Vibrio
Abstract: In the present paper 25 known thermolysin inhibitors were docked into thermolysin using the Internal Coordinate Mechanics (ICM™) software. Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout™ program. The docking studies indicated that all 25 inhibitors coordinated the catalytic zinc in bidentate or monodentate geometry. A ‘three-point’ pharmacophore model was proposed which consisted of a hydrophobic group, a negative ionizable group and a hydrogen bond acceptor group. Finally the pharmacophore model has been tested against a small compound library containing 18 highly, moderately, less active as well as inactive compounds. The screening indicated that the pharmacophore model could, identify highly active compounds in front of inactive or less active ones.
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Cite this article as:
T.H. Khan M., Wuxiuer Y. and Sylte I., Binding Modes and Pharmacophore Modelling of Thermolysin Inhibitors, Mini-Reviews in Medicinal Chemistry 2012; 12 (6) . https://dx.doi.org/10.2174/138955712800493799
DOI https://dx.doi.org/10.2174/138955712800493799 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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