Abstract
Finding and optimization of new HIV-1 integrase inhibitors is an important task due to the drawbacks of the existing HIV/AIDS therapy caused by the significant adverse effects, high cost of the treatment, and emerging resistance. In this study we have demonstrated potential of computer-assisted methods for finding and optimization of new HIV-1 integrase inhibitors blocking the 3′-processing reaction. Applicability of the specialized version of the computer program PASS for searching original inhibitors of 3′-processing reaction among commercially available samples of chemical compounds, belonging to a new chemical class, is shown. We compared the general pharmacological profiles calculated by PASS for the sets of original integrase inhibitors found in the study with those for known inhibitors published in literature. It was shown that the predicted average selectivity is close for the compounds from both sets, while the probability of predicted adverse/toxic effects is lower for the original compounds. Differences between the pharmacological profiles of original compounds and inhibitors of 3′-processing known in the literature pointed out to the essential novelty of our substances of the investigated chemical class. Significantly less deviations from the recommended values for QikProp parameters, which characterized the ADME properties, have been observed for the original compounds than for the integrase inhibitors published in literature. Thus, one can conclude that the original compounds look more prospective comparing to the earlier known inhibitors of 3′-processing.
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Original Russian Text © D.S. Druzhilovsky, D.A. Filimonov, Chenzhong Liao, Megan Peach, Mark Nicklaus, V.V. Poroikov, 2010, published in Biomeditsinskaya Khimiya.
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Druzhilovsky, D.S., Filimonov, D.A., Liao, C. et al. Computer-assisted search and optimization of new human immunodeficiency virus integrase inhibitors. Biochem. Moscow Suppl. Ser. B 4, 59–67 (2010). https://doi.org/10.1134/S1990750810010087
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DOI: https://doi.org/10.1134/S1990750810010087