AN EXHAUSTIVE REVIEW ON EMERGING DRUG TARGETS OF TUBERCULOSIS WITH SPECIAL EMPHASIS ON CELL WALL SYNTHESIS
Keywords:Cell wall synthesis, Enzymatic pathways, Mycolic acid, Tuberculosis
Tuberculosis (TB) is one of the top 10 causes of mortality and morbidity. Worldwide, yet, it has been over 60 years since a novel drug was introduced in market to treat the disease exclusively. Increased number of drug resistant TB cases has prompted the search for novel potent anti-TB drug. Mycobacterial cell wall has unique structure which provides integrity to the cell. The future development of new potent anti-TB drug targets is associated with the synthesis of various cell wall constituents; the structural and genetic information about mycobacterial cell wall envelope is now available. In the present review, we have focused on prospective drug targets that can be optimum triumph for successful drug candidate.
World Health Organisation. Global TUBERCULOSIS Report. Geneva, Switzerland, France: World Health Organisation; 2019.
Ahmad S, Mokaddas E. Current status and future trends in the diagnosis and treatment of drug-susceptible and multidrug-resistant Tuberculosis. J Infect Public Health 2014;7:75-91.
Palomino JC, Martin A. Drug resistance mechanisms in Mycobacterium tuberculosis. Antibiotics 2014;3:317-40.
Tripathi KD. Antitubercular drugs. In: Essentials of Medical Pharmacology. 7th ed. India: Jaypee Brother’s Medical Publishers (P) Ltd.; 2013. p. 765-79.
Gentry CA. Atypical Mycobacteria. In: Pharmacotherapy Self-assessment Program. 5th ed. United States: Learning Objectives; 2006. p. 99-126.
Foye WO, Lemke TL, Williams DA. Antimycobacterial agents. In: Foye’s Principles of Medicinal Chemistry. 6th ed. United States: Lippincott Williams and Wilkins; 2008. p. 1128-38.
Eduardo PD, Palomino JC. Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: Classical and new drugs. J Antimicrob Chemother 2011;66:1417-30.
Directorate General of Health Services-Central TB Division. Revised National TB control programme (India), India TB Report-2019, Annual Study Report. India: Directorate General of Health Services-Central TB Division; 2019.
Kaneko T, Cooper C, Mdluli K. Challenges and opportunities in developing novel drugs for TB. Future Med Chem 2011;3:1373-400.
Chiaradia L, Lefebvre C, Parra J, Marcoux J, Burlet-Schiltz O, Etienne G, et al. Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane. Sci Rep 2017;7:1-12.
Crick PJ. The cell-wall core of Mycobacterium tuberculosis in the context of drug discovery. Curr Top Med Chem 2007;7:475-88.
Singh G, Kumar A, Maan P, Kaur J. Cell wall associated factors of Mycobacterium tuberculosis as major virulence determinants: Current perspectives in drugs discovery and design. Curr Drug Targets 2017;18:1904-18.
Chatterjee D. The Mycobacterial cell wall: Structure, biosynthesis and sites of drug action. Curr Opin Chem Biol 1997;1:579-88.
Mdluli K, Spigelman M. Novel targets for Tuberculosis drug discovery. Curr Opin Pharmacol 2006;6:459-67.
LeMagueres P, Im H, Ebalunode J, Strych U, Benedik MJ, Briggs JM, et al. The 1.9 Å crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site. Biochemistry 2005;44:1471-81.
Halouska S, Chacon O, Fenton RJ, Zinniel DK, Barletta RG, Powers R. Use of NMR metabolomics to analyze the targets of d-cycloserine in Mycobacteria: Role of d-alanine racemase. J Proteome Res 2007;6:4608-14.
Prosser GA, Rodenburg A, Khoury H, de Chiara C, Howell S,Snijders AP, et al. Glutamate racemase is the primary target of β-chloro-D-alanine in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2016;60:6091-9.
David S. Synergic activity of d-cycloserine and β-chloro-d-alanine against Mycobacterium tuberculosis. J Antimicrob Chemother 2001;47:203-6.
Rombouts Y, Brust B, Ojha AK, Maes E, Coddeville B, Elass-Rochard E, et al. Exposure of Mycobacteria to cell wall-inhibitory drugs decreases production of arabinoglycerolipid related to mycolyl-arabinogalactan-peptidoglycan metabolism. J Biol Chem 2012;287:11060-9.
Martina B, Petronela D, Patrick J, Gladys C, Completo, Natisha L, et al. Galactosyl transferases in mycobacterial cell wall synthesis. J Bacteriol 2008;190:1141-45.
Giovanna R, Maria RP, Laurent RC, Giulia M, Andrea M, Claudia B. The DprE1 enzyme, one of the most vulnerable targets of Mycobacterium tuberculosis. Appl Microbiol Biotechnol 2013;97:8841-48.
Apoorva B, Virginie M, Gurdyal SB, William RJ, Laurent K. Micro review: The Mycobacterium tuberculosis FAS-II condensing enzymes: Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development. Mol Micro 2007;64:1442-54.
Christine EC, Adrienne CD, Katalin FM, Saida PS, Reza AG. Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: Catalase, peroxidase, and INH-NADH adduct formation activities. Protein Sci 2010;19:458-74.
Shrinivas DJ, Sheshagiri RD, Uttam AM, Tejraj MA, Venkatrao HK, Andanappa KG. Enoyl ACP reductase as effective target for the synthesized novel antitubercular drugs: A-state-of-the-art. Mini Rev Med Chem 2014;14:678-93.
Evans JC, Mizrahi V. Priming the Tuberculosis drug pipeline: New antimycobacterial targets and agents. Curr Opin Microbiol 2018;45:39-46.
Sarah AS, Tomohiko K, Noriaki I, Motohisa S, Anne EC, Edward K, et al. Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium tuberculosis by targeting FadD32. Proc Natl Acad Sci U S A 2013;110:11565-70.
Varela C, Rittmann D, Singh A, Krumbach K, Bhatt K, Eggeling L, et al. MmpL genes are associated with mycolic acid metabolism in Mycobacteria and Corynebacteria. Chem Biol 2012;19:498-506.
Eoh H, Brennan PJ, Crick DC. The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target. Tuberculosis 2009;89:1-11.
Boshoff HI, Barry CE. Is the Mycobacterial cell wall a hopeless drug target for latent Tuberculosis? Drug Discov Today Dis Mech 2006;3:237-45.
Marrakchi H, Lanéelle G, Quemard A. InhA, a target of the antituberculous drug isoniazid, is involved in a Mycobacterial fatty acid elongation system, FAS-II. Microbiology 2000;146:289-96.
Janin YL. Antituberculosis drugs: Ten years of research. Bioorg Med Chem 2007;15:2479-513.
Palomino J, Ramos D, da Silva P. New anti-Tuberculosis drugs: Strategies, sources and new molecules. Curr Med Chem 2009;16:1898-904.
Paulo F M O, Brigitte G, Alain C, Christiane A B, Jan M, Jana K, et al. Mechanochemical synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity. Molecules 2017;22:1-27.
Tahlan K, Wilson R, Kastrinsky DB, Nair V, Fischer E, Barnes SW, et al. Tuberculosis SQ109 targets mmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2012;56:1797-809.
North EJ, Jackson M, Lee RE. New approaches to target the mycolic acid biosynthesis pathway for the development of Tuberculosis therapeutics. Curr Pharm Des 2014;20:4357-78.
Engohang J. Antimycobacterial drugs currently in Phase II clinical trials and preclinical phase for Tuberculosis treatment. Expert Opin Investig Drugs 2012;21:1789-800.
Islam M, Hameed H, Mugweru J, Chhotaray C, Wang C, Tan Y, et al. Drug resistance mechanisms and novel drug targets for Tuberculosis therapy. J Genet Genomics 2017;44:21-37.
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