Molecules 2012, 17(12), 13740-13758; doi:10.3390/molecules171213740
Article

Generation of the First Structure-Based Pharmacophore Model Containing a Selective “Zinc Binding Group” Feature to Identify Potential Glyoxalase-1 Inhibitors

Received: 24 September 2012; in revised form: 15 November 2012 / Accepted: 19 November 2012 / Published: 22 November 2012
(This article belongs to the Section Medicinal Chemistry)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Within this study, a unique 3D structure-based pharmacophore model of the enzyme glyoxalase-1 (Glo-1) has been revealed. Glo-1 is considered a zinc metalloenzyme in which the inhibitor binding with zinc atom at the active site is crucial. To our knowledge, this is the first pharmacophore model that has a selective feature for a “zinc binding group” which has been customized within the structure-based pharmacophore model of Glo-1 to extract ligands that possess functional groups able to bind zinc atom solely from database screening. In addition, an extensive 2D similarity search using three diverse similarity techniques (Tanimoto, Dice, Cosine) has been performed over the commercially available “Zinc Clean Drug-Like Database” that contains around 10 million compounds to help find suitable inhibitors for this enzyme based on known inhibitors from the literature. The resultant hits were mapped over the structure based pharmacophore and the successful hits were further docked using three docking programs with different pose fitting and scoring techniques (GOLD, LibDock, CDOCKER). Nine candidates were suggested to be novel Glo-1 inhibitors containing the “zinc binding group” with the highest consensus scoring from docking.
Keywords: glyoxlase-1 enzyme; zinc binding group; GOLD; CDOCKER; molecular docking; 2D similarity search
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MDPI and ACS Style

Al-Balas, Q.; Hassan, M.; Al-Oudat, B.; Alzoubi, H.; Mhaidat, N.; Almaaytah, A. Generation of the First Structure-Based Pharmacophore Model Containing a Selective “Zinc Binding Group” Feature to Identify Potential Glyoxalase-1 Inhibitors. Molecules 2012, 17, 13740-13758.

AMA Style

Al-Balas Q, Hassan M, Al-Oudat B, Alzoubi H, Mhaidat N, Almaaytah A. Generation of the First Structure-Based Pharmacophore Model Containing a Selective “Zinc Binding Group” Feature to Identify Potential Glyoxalase-1 Inhibitors. Molecules. 2012; 17(12):13740-13758.

Chicago/Turabian Style

Al-Balas, Qosay; Hassan, Mohammad; Al-Oudat, Buthina; Alzoubi, Hassan; Mhaidat, Nizar; Almaaytah, Ammar. 2012. "Generation of the First Structure-Based Pharmacophore Model Containing a Selective “Zinc Binding Group” Feature to Identify Potential Glyoxalase-1 Inhibitors." Molecules 17, no. 12: 13740-13758.

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