Lead expansion and virtual screening of Indinavir derivate HIV-1 protease inhibitors using pharmacophoric - shape similarity scoring function |
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Authors: | Shityakov Sergey Dandekar Thomas |
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Institution: | Department of Bioinformatics, Biocenter of the University of Würzburg, 97074 Würzburg, Germany. shityakov@vim.uni-wuerzburg.de |
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Abstract: | Indinavir (Crivaxan®) is a potent inhibitor of the HIV (human immunodeficiency virus) protease. This enzyme has an important role in viral
replication and is considered to be very attractive target for new antiretroviral drugs. However, it becomes less effective due to highly resistant
new viral strains of HIV, which have multiple mutations in their proteases. For this reason, we used a lead expansion method to create a new set
of compounds with a new mode of action to protease binding site. 1300 compounds chemically diverse from the initial hit were generated and
screened to determine their ability to interact with protease and establish their QSAR properties. Further computational analyses revealed one
unique compound with different protease binding ability from the initial hit and its role for possible new class of protease inhibitors is discussed
in this report. |
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Keywords: | protease Indinavir lead expansion docking pharmacophore |
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