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Title |
Molecular docking analysis of nitisinone with homogentisate 1,2 dioxygenase
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Authors |
Narges Zolfaghari1,*
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Affiliation |
1National institute of genetic engineering and biotechnology, Tehran, Iran;
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Article Type |
Hypothesis
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Date |
Received April 12, 2017; Revised April 14, 2017; Accepted April 21, 2017; Published May 31, 2017
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Abstract |
Alkaptonuria is an inherited disease that is caused by homogenticate accumulation. Deficiency or mutation in Homogentisate 1,2 dioxygenase gene (chromosome 3q21-q23) leads to production of incorrectly folded or truncated enzyme. Several studies indicated that competitive inhibitors of Homogentisate 1,2 dioxygenase like Nitisinone could be used for Alkaptonuria treatment. Therefore, it is of interest to design better inhibitors of the enzyme. We used subset 3_p.0.5 from Zinc database as the virtual screening library by PyRx software relaying on Lamarckian genetics algorithm. Top 10 hits with more efficient binding affinity were analyzed and hit No#5 and No#7 was selected for further design. In Lig No#5, we decreased the hydrophobicity by adding oxygen in the hydrophobic tail of the molecule at positions C5 and C10. The new compound of (2Z, 5Z, 8Z)-6,9-Dihydroxy-2-(2-hydroxy-5-oxo-1,3-cyclohexadien-1-yl)-2,5,8-decatrienoic acid satisfied Lipinski rules as well as PhysChem and FafDrugs filters. Moreover, the modified version of Lig No# 7 with the IUPAC name of [2-(Carboxymethyl)-3,5-dihydroxyphenyl] acetic acid satisfies the Lipisnki, FafDrugs and Physchem.
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Keywords |
Alkaptonuria, Lipinski rules, drug design
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Citation |
Zolfaghari, Bioinformation 13(5): 136-139 (2017)
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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.
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