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Title |
Lead identification and optimization of novel collagenase inhibitors; pharmacophore and structure based studies |
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Authors |
Sukesh Kalva1, S Vadivelan2, 3*, Ramadevi Sanam2, Sarma ARP Jagarlapudi2, Lilly M Saleena1* |
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Affiliation |
1Department of Bioinformatics, SRM University, SRM Nagar, Kattankulathur - 603 203, Kancheepuram District, Chennai, India; 2Informatics, GVK Biosciences Private Limited, 443, Guna Complex, 9th Floor Annexe I Building, Anna Salai, Teynampet; 3E.G.S.Pillay College of Pharmacy, Old Nagore Road, Nagapattinam 611 002, Tamilnadu, India.
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lmsaleena@ktr.srmuniv.ac.in; *Corresponding author
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Article Type |
Hypothesis
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Date |
Received March 14, 2012; Accepted April 03, 2012; Published April 13, 2012 |
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Abstract |
In this study, chemical feature based pharmacophore models of MMP-1, MMP-8 and MMP-13 inhibitors have been developed with the aid of HypoGen module within Catalyst program package. In MMP-1 and MMP-13, all the compounds in the training set mapped HBA and RA, while in MMP-8, the training set mapped HBA and HY. These features revealed responsibility for the high molecular bioactivity, and this is further used as a three dimensional query to screen the knowledge based designed molecules. These pharmacophore models for collagenases picked up some potent and novel inhibitors. Subsequently, docking studies were performed for the potent molecules and novel hits were suggested for further studies based on the docking score and active site interactions in MMP-1, MMP-8 and MMP-13.
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Keywords |
Collagenases, Osteoarthritis, S1' loop, Pharmacophore, Induced Fit, HypoGen.. |
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Citation |
Kalva et al.
Bioinformation 8(7): 301-308 (2012) |
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |