In-Silico Design and Study of Novel Tetrahydro-β-Carbolines as Inhibitor of HIV-1 Reverse Transcriptase

Abstract

Abstract

In the present study, we have designed 50 novel tetrahydro-β-carboline derivatives as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Docking studies of 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 were derived through online servers Molinspiration and Osiris property explorer respectively. Docking parameters such as binding free energy and predicted inhibitory constant (Ki) values of designed analogs were compared with standard drug Efavirenz and TNK-651. Among the designed analogs, TBB-III-29, TBB-III-33, TBB-III-39, TBB-III-42, TBB-III-44, TBB-III-45, TBB-III-46, TBB-III-49 and TBB-III-50 showed significant binding free energy and predicted inhibitory constants with that of standard drug Efavirenz and TNK-651. These results also indicate that, the designed analogs adopt a similar orientation and share the same binding mode as that of some classical non-nucleoside reverse transcriptase inhibitors (NNRTIs) within the active site of non-nucleoside inhibitory binding pocket (NNIBP) of HIV-1 reverse transcriptase.

Keywords: AIDS, HIV-1 reverse transcriptase, docking, molecular properties, tetrahydro-β-carboline

Cite this Article

Ashok Penta, Subhash Chander, Sankaranarayanan Murugesan. In-Silico Design and Study of Novel Tetrahydro-β-Carbolines as Inhibitor of HIV-1 Reverse Transcriptase. Research & Reviews: A Journal of Drug Design & Discovery. 2016; 3(1): 19–30p.