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Molecular Docking Studies of Novel Pyrazole Analogs as Possible HIV-1-RT Inhibitors
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1  Department of pharmaceutical sciences and Technology, Birla Institute of Technology, Ranchi, INDIA

Abstract: The human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS) that has been affected 34 million people worldwide. Though an unprecedented growth has been taken place in the development of anti-HIV drugs during the last two decades, there is still no cure for this deadly disease. Cross resistance to anti HIV drugs is also a major concern in the development of anti AIDS pharmaceuticals. Therefore, nowadays studies are being focused mainly on the development of newer drugs capable of inhibiting resistant mutants. HIV-1-RT is one of the major targets for the development of newer molecular entities (NMEs) for the treatment of HIV/AIDS. Inhibitors of HIV-1-RT are classified as nucleoside reverse transcriptase inhibitors (NRTIs) and non nucleoside reverse transcriptase inhibitors (NNRTIs). A compound incorporating the pyrazole structural unit, lersiverine was reported recently, as a NNRTI. The objective of this study was to elucidate the binding mode analysis of novel pyrazole analogs in the non nucleoside inhibitory binding pocket of reverse transcriptase (PDB ID IRT2). Molecular docking studies of 484 novel pyrazole analogs were performed by Glide program in the NNIBP of HIV-1 reverse transcriptase (PDB code 1RT2).The   Novel pyrazole analogs bearing different substituted aryl groups were designed The following   eight  compounds  with aryl substituents like R=2,5-2CH3 &R1= m-OCH3 , R=H &R1=m-OCH3,R=H &R1=m-CH3, R=o-Cl &R1=m-OCH3, R=o-Cl &R1=p-OCH3, R=m-CH3 &R1=m-CH3, R=m-Cl &R1=m-Cl, R=m-Cl &R1=2,4-2NO2, exhibited highest docking score in the NNIBP of  IRT2 . Thus, it is evident that this kind of scaffold with hydrophobic and electron donating or electron withdrawing groups substituted  in the phenyl rings can be exploited for the  development of  novel HIV-1-RT2 inhibitors which can facilitate better patient adherence and also inhibit the resistant strains of HIV.
Keywords: HIV-1 Reverse Transcriptase; pyrazole; NNRTIs; 1RT2; docking