Molecular docking and in silico studies on analogues of 2-methylheptyl isonicotinate with DHDPS enzyme of Mycobacterium
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Med Chem Res (2013) 22:4755–4765 DOI 10.1007/s00044-013-0488-5
ORIGINAL RESEARCH
Molecular docking and in silico studies on analogues of 2-methylheptyl isonicotinate with DHDPS enzyme of Mycobacterium tuberculosis Salam Pradeep Singh • Bolin Kumar Konwar • Rajib Lochan Bezbaruah • Tarun Chandra Bora
Received: 4 August 2012 / Accepted: 11 January 2013 / Published online: 23 January 2013 Ó Springer Science+Business Media New York 2013
Abstract Mycobacterium tuberculosis and other strains of mycobacteria cause tuberculosis which has infected onethird of the world’s population. Moreover, there has been increase in multidrug-resistant strains which spotlights the need for a new anti-tuberculosis drug. The cell wall of mycobacteria is characterised by high diaminopimelic acid (DAP) content—an intermediate of the (S)-lysine biosynthetic pathway and dihydrodipicolinate synthase (DHDPS) enzyme catalyses the first unique reaction of this biosynthesis. Interestingly, the gene knockout experiment demonstrates the essentiality of the DAP pathway, where the absence of DAP results in cell lysis and death. Because of this importance, any inhibitor of DHDPS enzyme may indicate a new class of anti-tubercular agent. In this perspective, the aim of the present study is to focus on the molecular docking analysis of DHDPS enzyme against the analogues of 2-methylheptyl isonicotinate—a compound having strong antibacterial property against Mycobacterium tuberculosis. The analogues used in the present study were retrieved from the NCBI PubChem database subject to Lipinski rule of five filters which would make the analogues like an orally active drug. Further, the top docked compounds at the active site of the DHDPS enzyme were analysed for ADME-Toxicity prediction.
S. P. Singh (&) B. K. Konwar Bioinformatics Infrastructure Facility, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, India e-mail: [email protected] R. L. Bezbaruah T. C. Bora Bioinformatics Infrastructure Facility, Biotechnology Division, North-East Institute of Science and Technology, Jorhat, Assam, India
Keywords DHDPS enzyme Molecular docking 2-Methylheptyl isonicotinate ADME-toxicity
Introduction Tuberculosis is a common and infectious disease caused by various strains of mycobacteria, mostly Mycobacterium tuberculosis [Mtb] (Kumar et al., 2007). It usually attacks the lungs (Tripathi et al., 2005) and spreads through the air when people who have an active infection cough, sneeze or transfer their saliva through the air (Konstantinos, 2010). Jasmer et al. (2002) reported that one-third of the world’s population have been infected with Mycobacterium tuberculosis (Jasmer et al., 2002) and new infections occur at the rate of one per second (Tuberculosis, 2007). There are also reports of an estimated 13.7 million people having active tuberculosis disease, with 9.3 million new cases and 1.8 million deaths in 2007 (World Health Organization, 2009). Thus, the increase in tuberculosis cases worldwide, particularly among immu
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