3D-QSAR and Molecular Docking Studies of Triazol-Cycloalkanol Derivatives Used as Potent 3-Dehydroquinase II Inhibitors Against Mycobacterium tuberculosis

Abstract

Tuberculosis is a life threatening infectious disease caused by gram positive bacteria mycobacterium tuberculosis. Emergence of drug resistance, multi drug resistance and extensively drug resistance strain of mycobacterium make the situation more worst. It increases the mortality rate of tuberculosis patient, time duration and cost of treatment. Various inhibitors and drug molecules are designed to combat this fatal disease. Enzymes of shikimate pathway are responsible for production of essential amino acid for mycobacterium and are vital for survival of micro-organism into the host. Various enzymes of this pathway are targeted now days to find new anti-tubercular drugs. In this study we perform the 3D QSAR analysis of inhibitors of 3-Dehydroquinase (third enzyme of shikimate pathway) by k-nearest neighbour (kNN-MFA) with Step Wise (SW), Simulated Annealing (SA), Genetic Algorithm (GA) approach. A data set of 22 triazole-cycloalkanol derivative is selected and divided into training and test set molecule to generate various models. The best model contains seventeen training and five testset molecules with good internal and external predictivity. Model is statistically good as it show internal predictivity 82% (q²=0.8270) and external predictivity 94% (r²=0.9491). Model shows that the electrostatic interaction plays an important role in determining 3-dehydroquinase inhibitory activity. Designing of new inhibitor molecules were perform by substituting suitable group at places shown in model. The drug likenesses of these compounds were checked by ADME property prediction and explore their interaction with 3-Dehydroquinase II by molecular docking studies.

Keywords: 3D QSAR, kNN, triazolecycloalkanol derivative, docking

Cite this Article

Anand Kumar Gupta, Mishra BN, Vivek Srivastava. 3D-QSAR and Molecular Docking Studies of Triazol-Cycloalkanol Derivatives Used as Potent 3-Dehydroquinase II Inhibitors against Mycobacterium tuberculosis. Research & Reviews: A Journal of Biotechnology. 2015; 5(3): 18–28p.