Abstract
In the present study, we have designed 50 novel 1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid analogs as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Docking studies of the designed analogs were performed by molecular modeling software autodock 4.2 using HIV-1 reverse transcriptase (PDB ID: 1rt2) as receptor. Lipinski rule of five parameters and toxicity parameters was derived through online servers like molinspiration and Osiris property explorer. Docking parameters such as binding free energy and predicted inhibitory constant (Ki) values of the designed analogs were compared with standard drug efavirenz and co-crystallized ligand TNK-651. Among the designed analogs, TBB-II-5, TBB-II-7, TBB-II-21, TBB-II-22, TBB-II-24, TBB-II-25, TBB-II-26, TBB-II-33, TBB-II-37, TBB-II-38, and TBB-II-43 showed significant and comparable binding-free energy and predicted inhibitory constant values as that of standard drug efavirenz and TNK-651. These results indicate that, the designed analogs adopt a similar orientation and share the same binding mode as that of some of the classical non-nucleoside reverse transcriptase inhibitors within the active site of non-nucleoside inhibitory binding pocket of HIV-1 reverse transcriptase.
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We thank BITS-Pilani for providing the facilities to do this work. One of the authors Ashok P acknowledges Council of Scientific and Industrial Research for financial support in the form Senior Research Fellowship.
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Penta, A., Chander, S., Ganguly, S. et al. De novo design and in-silico studies of novel 1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid derivatives as HIV-1 reverse transcriptase inhibitors. Med Chem Res 23, 3662–3670 (2014). https://doi.org/10.1007/s00044-014-0945-9
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DOI: https://doi.org/10.1007/s00044-014-0945-9