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An in Silico Approach for Prioritizing Drug Targets in Metabolic Pathway of Mycobacterium Tuberculosis

Authors: Baharak Khoshkholgh-Sima, Soroush Sardari, Jalal Izadi Mobarakeh, Ramezan Ali Khavari-Nejad


There is an urgent need to develop novel Mycobacterium tuberculosis (Mtb) drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria. Our study structured based on integrated analysis of metabolic pathways, small molecule screening and similarity Search in PubChem Database. Metabolic analysis approaches based on Unified weighted used for potent target selection. Our results suggest that pantothenate synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl transferase (panB) as a appropriate drug targets. In our study, we used pantothenate synthetase because of existence inhibitors. We have reported the discovery of new antitubercular compounds through ligand based approaches using computational tools.

Keywords: In Silico, Ligand-based Virtual Screening, Metabolic Pathways, Mycobacterium tuberculosis

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[1] T. R. Ioerger, and J. C. Sacchettini, "Structural genomics approach to drug discovery for Mycobacterium tuberculosis," CURR OPIN MICROBIOL J., vol. 12, pp. 318-325, 2009.
[2] S. K. Kushwaha, and M. Shakya, "Protein interaction network analysis- Approachforpotentialdrugtarget identification in Mycobacterium tuberculosis,"-Theor. Biol. J., vol. 262, pp. 284-294, 2010.
[3] Y. Zhang, K. Post-Martens, and S. Denkin, "New drug candidates and therapeutic targets for tuberculosis therapy," DDT J., vol. 11, no. 1/2, pp. 21-27, Jan. 2006.
[4] G. J. Crowther et al. ,"Identification of Attractive Drug Targets in Neglected-Disease Pathogens Using an In Silico Approach," PLoS Negl Trop Dis J., vol. 4, no. 8, e804, Aug. 2010.
[5] S. Velaparthi et al., "5-tert-Butyl-N-pyrazol-4-yl-4,5,6,7- tetrahydrobenzo
[d]isoxazole-3-carboxamide derivatives as novel potent inhibitors of Mycobacterium tuberculosis pantothenate pynthetase: initiating a quest for new antitubercular drugs," J. Med. Chem, vol. 51, pp. 1999-2002, Nov. 2007.
[6] Fabrizio Manetti et al., "Ligand-based virtual screening, parallel solution-phase and microwave-assisted synthesis as tools to identify and synthesize new inhibitors of Mycobacterium tuberculosis," ChemMedChem J., vol. 1, pp. 973 - 989, 2006.
[7] S. Ekins, J. S. Freundlich5, I. Choi, M. Sarker,-and C. Talcott, " Computational databases, pathway and cheminformatics tools for tuberculosis drug discovery," Trends Microbiol. J., vol.764, pp. 1-10, 2010.
[8] Q. Gao, K.E. Kripke, A.J. Saldanha, W. Yan, S. Holmes, P.M. Small,"Gene expression diversity among Mycobacterium tuberculosis clinical isolates," Microbiology J., vol. 151, pp.5-14, 2005.
[9] H. Rachman et al., "Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary tuberculosis," Infect. Immun. J., vol. 74, no. 2, pp. 1233-1242, 2006.
[10] H.I. Boshoff et al., "The transcriptional responses of-Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action," The Journal of Biological Chemistry J., vol. 279, no. 38, pp. 40174-40184, 2004.
[11] S. Anishetty, M. Pulimi, and G. Pennathur., "Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis," Comput. Biol. Chem. J., vol. 29, no. 5, pp. 368-378, 2005.
[12] K. Raman, K. Yeturu, and N. Chandra., "targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis," BMC Syst. Biol. J., vol. 2, no. 109, p. 21, 2008.
[13] S. Hasan, S. Daugelat, P.S. Srinivasa Rao, and M. Schreiber., " Schreiber: Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis," PLoS Comput. Biol. J., vol. 2, no. 6, e61, 2006.
[14] V.K. Sambandamurthy et al., "A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis," Nat. Med. J., vol. 8, no.10, pp. 1171-1174, 2002.
[15] M. Muddassar et al., " Identification of novel antitubercular compounds through hybrid virtual screening approach," Bioorganic & Medicinal Chemistry J., vol. 18, pp. 6914-6921, 2010.
[16] L. A. Basso et al., " The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases - A Review," Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 100, no. 6, pp. 475-506, Oct. 2005.
[17] L. Respicio et al., " Characterizing septum inhibition in Mycobacterium tuberculosis for novel drug discovery," Tuberculosis J., vol. 88, pp.420- 429, 2008.
[18] K. Duncan, "Identification and validation of novel drug targets in tuberculosis," Curr. Pharm. J., vol. 10, PP. 3185-3194, Des. 2004.
[19] C.E. Barry, R.A. Slayden, A.E. Sampson, and R.E. Lee, " Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs," Biochem. Pharmacol. J., Vol. 59,-pp. 221- 231, 2000.