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Molecular Docking Studies in Multitarget Antitubercular Drug Discovery

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Multi-Target Drug Design Using Chem-Bioinformatic Approaches

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease with high levels of mortality worldwide, currently with approximately 6.3 million new cases per year that often present resistance to both first- and second-line drugs. These high rates of incidence are due to several factors including bacterial resistance, AIDS cases, and latent tuberculosis that can reoccur in the patient. Among methods used in the search for new tuberculosis drugs are in silico or CADD (computer-aided drug design) studies, which are increasingly being employed in industry and universities. They investigate molecular interactions in order to understand both the structural characteristics of compounds and their activities through virtual manipulation of their three-dimensional (3D) molecular structures, as is the case with molecular docking. Such analyses allow extraction of information and characteristics relevant to compound activity, as well as to predict potential application. In our studies, we discovered antituberculotic activity in various derivatives: thiophenes, sulfonamides, chalcones, nitroimidazoles, benzimidazoles, peptides, and quinolones with action in several specific M. tuberculosis enzymes. For each derivative, multitarget activity was evaluated in molecular docking studies to select promising compounds with activity(s) against tuberculosis. This chapter will present and discuss molecular docking studies within the bacillus complex, the pharmacological potential of multitarget compounds, and new promising drug candidates with high levels of specificity.

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References

  1. Brosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C, Eiglmeier K, Garnier T, Gutierrez C, Hewinson G, Kremer K, Parsons LM, Pym AS, Samper S, Soolingen D, Cole ST (2002) A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A 99(6):3684–3689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sensi P, Grass IGG (1996) Antimycobacterial agents. In: Wolff ME (ed) Burger’s medicinal chemistry and drug discovery, 5th edn. Wiley, New York

    Google Scholar 

  3. World Health Organization (2017) Global TB Rep. 2017. http://apps.who.int/iris/bitstream/10665/259366/1/9789241565516-eng.pdf?ua=1. Accessed Aug 2017

  4. Junior ALR, Netto AR, Castilho EA (2014) Spatial distribution of the human development index, HIV infection and AIDS-Tuberculosis comorbidity: Brazil, 1982–2007. Rev Bras Epidemiol 17:204–215

    Article  Google Scholar 

  5. World Health Organization (2016) Global TB report. http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf. Accessed Aug 2017

  6. The World Health Organization (WHO) (2015) Global tuberculosis report. http://www.who.int/tb/publications/global_report/en/. Accessed Apr 2017

  7. Hatfull GF, Jacobs WR Jr (2014) Molecular genetics of mycobacteria. American Society for Microbiology Press, Washington, DC

    Book  Google Scholar 

  8. Zhang HN, Xu ZW, Jiang HW, Wu FL, He X, Liu Y, Guo SJ, Li Y, Bi LJ, Deng JY, Zhang XE, Tao SC (2017) Cyclic di-GMP regulates Mycobacterium tuberculosis resistance to ethionamide. Sci Rep 7(1):5820–5832

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Joshi RR, Barchha A, Khedkar VM, Pissurlenkar RRS, Sarkar S, Sarkar D, Joshi RR, Joshi RA, Shah AK, Coutinho EC (2015) Targeting dormant tuberculosis bacilli: results for molecules with a novel pyrimidone scaffold. Chem Biol Drug Des 85(2):201–207

    Article  CAS  PubMed  Google Scholar 

  10. Parida SK, Axelsson-Robertson R, Rao MV, Singh N, Master I, Lutckii A, Keshavjee S, Ansersson J, Zumla A, Maeurer M (2015) Totally drug-resistant tuberculosis and adjunct therapies. J Intern Med 277(4):388–405

    Article  CAS  PubMed  Google Scholar 

  11. Sotgiu G, Centis R, D’Ambrosio L, Alffenaar JWC, Anger HA, Caminero JA, Castiglia P, Lorenzo S, Ferrara G, Koh WJ, Schecter GF, Shim TS, Singla R, Skrahina A, Spanevello A, Udwadia ZF, Villar M, Zampogna E, Zellweger JP, Zumla A, Migliori GB (2012) Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J 40(6):1430–1442

    Article  CAS  PubMed  Google Scholar 

  12. Udwadia ZF, Amale RA, Ajbani KK, Rodrigues CS (2012) Nomenclature of drug-resistant tuberculosis. Lancet Infect Dis 13(11):917

    Article  Google Scholar 

  13. Yew WW, Leung CC (2008) Update in tuberculosis 2007. Am J Respir Crit Care Med 177(5):479–485

    Article  CAS  PubMed  Google Scholar 

  14. Goldman RC, Plumley KV, Laughon BE (2007) The evolution of extensively drug resistant tuberculosis (XDR-TB): history, status and issues for global control. Infect Disord Drug Targets 7(2):73–91

    Article  CAS  PubMed  Google Scholar 

  15. Espinal MA (2003) The global situation of MDR-TB. Tuberculosis 83(1):44–51

    Article  PubMed  Google Scholar 

  16. Yildirim MA, Goh KI, Cusick ME, Barabasi AL, Vidal M (2007) Drug-target network. Nat Biotechnol 25(10):1119–1126

    Article  CAS  PubMed  Google Scholar 

  17. Lavecchia A, Di Giovanni C (2013) Virtual screening strategies in drug discovery: a critical review. Curr Med Chem 20(23):2839–2860

    Article  CAS  PubMed  Google Scholar 

  18. Pei J, Yin N, Ma X, Lai L (2014) Systems biology brings new dimensions for structure-based drug design. J Am Chem Soc 136:11556–11565

    Article  CAS  PubMed  Google Scholar 

  19. Morphy R, Rankovic Z (2005) Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem 48:6523–6543

    Article  CAS  PubMed  Google Scholar 

  20. Zhang W, Pei J, Lai L (2017) Computational multitarget drug design. J Chem Inf Model 57:403–412

    Article  CAS  PubMed  Google Scholar 

  21. McBryde ES, Meehan MT, Doan TN, Ragonnet R, Marais BJ, Guernier V, Trauer JM (2017) The risk of global epidemic replacement with drug-resistant Mycobacterium tuberculosis strains. Int J Infect Dis 56:14–20

    Article  PubMed  Google Scholar 

  22. Ramaswamy SV, Amin AG, Göksel S, Stager CE, Dou SJ, Sahly HE, Moghazeh SL, Kreiswirth BN, Musser JM (2000) Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 44:326–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bhatt JD, Chudasama CJ, Patel KD (2015) Pyrazole clubbed triazolo [1, 5-α] pyrimidine hybrids as an anti-tubercular agent: synthesis, in vitro screening and molecular docking study. Bioorg Med Chem 23(24):7711–7716

    Article  CAS  PubMed  Google Scholar 

  24. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lou Z, Zhang X (2010) Protein targets for structure-based anti Mycobacterium tuberculosis drug discovery. Protein Cell 1(5):435–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chetty S, Ramesh M, Pillay AS, Soliman MES (2017) Recent advancements in the development of anti-tuberculosis drugs. Bioorg Med Chem Lett 27(3):370–386

    Article  CAS  PubMed  Google Scholar 

  27. Yuriev E, Agostino M, Ramsland PA (2011) Challenges and advances in computational docking: 2009 in review. J Mol Recognit 24(2):149–164

    Article  CAS  PubMed  Google Scholar 

  28. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393(6685):537–544

    Article  CAS  PubMed  Google Scholar 

  29. Ananthan S, Faaleolea ER, Goldman RC, Hobrath JV, Kwong CD, Laughon BE, Maddry JA, Mehta A, Rasmussen L, Reynolds RC, Secrist JA, Shindo N, Showe DN, Sosa MI, Sunling WJ, White EL (2009) High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv. Tuberculosis 89:335–353

    Article  CAS  Google Scholar 

  30. Foo CSY, Lechartier B, Kolly GS, Röttger SB, Neres J, Rybniker J, Lupien A, Sala C, Piton J, Cole ST (2016) Characterization of DprE1-mediated benzothiazinone resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 60(11):6451–6459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. New Drugs TB. https://www.newtbdrugs.org/pipeline/compounds. Accessed 15 Sept 2017

  32. Mikusova K, Huang H, Yagi T, Holsters M, Vereecke D, Haeze WD, Scherman MS, Brennan PJ, Mcneil MR, Crick DC (2005) Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of Mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose. J Bacteriol 187(23):8020–8025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Batt SM, Jabeen T, Bhowruth V, Quill L, Lund PA, Eggeling L, Alderwick LJ, Fütterer K, Besra GS (2012) Structural basis of inhibition of Mycobacterium tuberculosis DprE1 by benzothiazinone inhibitors. Proc Natl Acad Sci U S A 109(28):11354–11359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Neres J, Pojer F, Molteni E, Chiarelli LR, Dhar N, Boy-röttger S, Buroni S, Fullam E, Degiacomi G, Lucarelli AP, Read RJ, Zanoni G, Edmondson DE, Rossi E, Pasca MR, Mckinney JD, Dyson PJ, Riccardi G, Mattevi A, Cole ST, Binda C (2012) Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis. Sci Transl Med 4(150):121–150

    Article  CAS  Google Scholar 

  35. Gao C, Ye TH, Wang NY, Zeng XX, Zhang LD, Xiong Y, You XY, Xia Y, Peng CT, Zuo WQ, Wei Y, Yu LT (2013) Synthesis and structure–activity relationships evaluation of benzothiazinone derivatives as potential anti-tubercular agents. Bioorg Med Chem Lett 23(17):4919–4922

    Article  CAS  PubMed  Google Scholar 

  36. Tiwari R, Miller PA, Chiarelli LR, Mori G, Sarkan M, Centarova I, Cho S, Mikusova K, Franzblau SG, Oliver AG, Miller MJ (2016) Design, syntheses, and anti-TB activity of 1,3-benzothiazinone azide and click chemistry products inspired by BTZ043. Med Chem Lett 7:266–270

    Article  CAS  Google Scholar 

  37. Riccardi G, Pasca MR, Chiarelli LR, Manina G, Mattevi A, Binda C (2012) The DprE1 enzyme, one of the most vulnerable targets of Mycobacterium tuberculosis. Appl Microbiol Biotechnol 97(20):8841–8848

    Article  CAS  Google Scholar 

  38. Trefzer C, Gonzalez MR, Hinner MJ, Schneider P, Makarov V, Cole ST, Johnsson K (2010) Benzothiazinones: prodrugs that covalently modify the decaprenylphosphoryl-β-D-ribose 2′-epimerase DprE1 of Mycobacterium tuberculosis. J Am Chem Soc 132:13663–13665

    Article  CAS  PubMed  Google Scholar 

  39. Trefzer C (2012) DprE1 as a drug target from Mycobacterium tuberculosis. EPFL, Lausanne

    Google Scholar 

  40. Bouhss A, Mengin-Lecreulx D, Blanot D, van Heijenoort J, Parquet C (1997) Invariant amino acids in the Mur peptide synthetases of bacterial peptidoglycan synthesis and their modification by site-directed mutagenesis in the UDP-MurNAc:L-alanine ligase from Escherichia coli. Biochemistry 36:11556–11563

    Article  CAS  PubMed  Google Scholar 

  41. Eveland SS, Pompliano DL, Anderson MS (1997) Conditionally lethal Escherichia coli murein mutants contain point defects that map to regions conserved among murein and folyl poly-gamma-glutamate ligases: identification of a ligase superfamily. Biochemistry 36:6223–6229

    Article  CAS  PubMed  Google Scholar 

  42. Walsh AW, Falk PJ, Thanassi J, Discotto L, Pucci MJ, Ho HT (1999) Comparison of the D-glutamate adding enzymes from selected gram-positive and gram-negative bacteria. J Bacteriol 181:5395–5401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zoeiby A, Sanschagrin F, Levesque RC (2003) Structure and function of the Mur enzymes: development of novel inhibitors. Mol Microbiol 47:1–12

    Article  PubMed  Google Scholar 

  44. Smith CA (2006) Structure, function and dynamics in the mur family of bacterial cell wall ligases. J Mol Biol 362:640–655

    Article  CAS  PubMed  Google Scholar 

  45. Munshi T, Gupta A, Evangelopoulos D, Guzman JD, Gibbons S, Keep NH, Bhakta S (2013) Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell wall peptidoglycan in Mycobacterium tuberculosis. PLoS One 8(3):60143

    Article  CAS  Google Scholar 

  46. Eniyan K, Kumar A, Rayasam GV, Perdih A, Bajpai U (2016) Development of a one-pot assay for screening and identification of Mur pathway inhibitors in Mycobacterium tuberculosis. Sci Rep 6:35134–35146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Deva T, Baker EN, Squire CJ, Smith CA (2006) Structure of Escherichia coli UDP-N-acetylmuramoyl:L-alanine ligase (MurC). Acta Crystallogr D Biol Crystallogr 62:1466–1474

    Article  CAS  PubMed  Google Scholar 

  48. Basavannacharya C, Robertson G, Munshi T, Keep NH, Bhakta S (2010) ATP-dependen MurE ligase in Mycobacterium tuberculosis: biochemical and structural characterisation. Tuberculosis 90(1):16–24

    Article  CAS  PubMed  Google Scholar 

  49. Silhavy TJ, Kahne D, Walker S (2010) The bacterial cell envelope. Cold Spring Harb Perspect Biol 2:1–17

    Article  CAS  Google Scholar 

  50. Sinha S, Kosalai K, Arora S, Namane A, Sharma P, Gaikwad AN, Brodin P, Cole ST (2005) Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics. Microbiolgy 151:2411–2419

    Article  CAS  Google Scholar 

  51. Singh R, Manjunatha U, Boshoff HI, Ha YH, Niyomrattanakit P, Ledwidge R, Dowd CS, Lee IY, Kim P, Zhang L, Kang S, Keller TH, Jiricek J, Barry CE (2008) PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science 322:1392–1395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Manjunatha U, Boshoff HI, Barry CE (2009) The mechanism of action of PA-824: novel insights from transcriptional profiling. Commun Integr Biol 2:215–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Somasundaram S, Anand RS, Venkatesan P, Paramasivan CN (2013) Bactericidal activity of PA-824 against Mycobacterium tuberculosis under anaerobic conditions and computational analysis of its novel analogues against mutant Ddn receptor. Microbiology 13(1):1392–1395

    Google Scholar 

  54. Kim P, Zhang L, Manjunatha UH, Singh R, Patel S, Jiricek J, Keller TH, Boshoff HI, Barry CE III, Dowd CS (2009) Structure–activity relationships of antitubercular nitroimidazoles. Structural features associated with aerobic and anaerobic activities of 4- and 5-nitroimidazoles. J Med Chem 52:1317–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rani C, Mehra R, Sharma R, Chib R, Wazir P, Nargotra A, Khan IA (2015) High-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU. Tuberculosis 95(6):664–677

    Article  CAS  PubMed  Google Scholar 

  56. Mengin-Lecreulx D, van Heijenoort J (1994) Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis. J Bacteriol 176:5788–5795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhang Z, Bulloch EM, Bunker RD, Baker EN, Squire CJ (2009) Structure and function of GlmU from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr 65:275–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, McKenney K, Sutton G, FitzHugh W, Fields C, Gocayne JD, Scott J, Shirley R, Liu LI, Glodek A, Kelley JM, Weidman JF, Phillips CA, Springgs T, Hedblom E, Cotton MD, Utterback TR, Hanna MC, Nguyen DT, Saudek DM, Brandon RC, Fine LD, Fritchman JL, Fuhrmann JL, Geoghager NSM, Gnehm CL, McDonald LA, Small KV, Fraser CM, Smith HO, Venter JC (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae RD. Science 269:496–512

    Article  CAS  PubMed  Google Scholar 

  59. Hove-Jensen B (1992) Identification of tms-26 as an allele of the gcad gene, which encodes N-acetylglucosamine-1-phosphate uridyltransferase in Bacillus subtilis. J Bacteriol 174:6852–6856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Olsen LR, Vetting MW, Roderick SL (2007) Structure of the E. coli bifunctional GlmU acetyltransferase active site with substrates and products. Protein Sci 16:1230–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sharma R, Lambu MR, Jamwal U, Rani C, Chib R, Wazir P, Mukherjee D, Chaubey A, Kan IA (2016) Escherichia coli N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) inhibitory activity of terreic acid isolated from Aspergillus terreus. J Biomol Screen 21(4):342–353

    Article  CAS  PubMed  Google Scholar 

  62. Gavalda S, Léger M, van der Rest B, Stella A, Bardou F, Montrozier H, Chalut C, Burlet-Schiltz O, Marrakchi H, Daffé M, Quémard A (2009) The Pks13/FadD32 crosstalk for the biosynthesis of mycolic acids in Mycobacterium tuberculosis. J Biol Chem 284:19255–19264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Maier T, Jenni S, Ban N (2006) Architecture of mammalian fatty acid synthase at 4.5 Å resolution. Science 311:1258–1262

    Article  CAS  PubMed  Google Scholar 

  64. Khosla C (2009) Structures and mechanisms of polyketide synthases. J Org Chem 74:6416–6420

    Article  CAS  PubMed  Google Scholar 

  65. Portevin D, de Sousa-D’Auria C, Houssin C, Grimaldi C, Chami M, Daffé M, Guilhot C (2004) A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms. Proc Natl Acad Sci U S A 101(1):314–319

    Article  CAS  PubMed  Google Scholar 

  66. Khosla C, Tang Y, Chen AY, Schnarr NA, Cane DE (2007) Structure and mechanism of the 6-deoxyerythronolide B synthase. Annu Rev Biochem 76:195–221

    Article  CAS  PubMed  Google Scholar 

  67. Tang Y, Chen AY, Kim CY, Cane DE, Khosla C (2007) Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. Chem Biol 14:931–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Fernandes GFS, Chin CM, Santos JL (2017) Potenciais alvos moleculares para o desenvolvimento de novos fármacos antituberculose. Quim Nova 40(5):572–585

    CAS  Google Scholar 

  69. Bloch K (2006) Control mechanisms for fatty acid synthesis in Mycobacterium smegmatis. Wiley, New York

    Google Scholar 

  70. Jackowski S, Rock CO (1987) Acetoacetyl-acyl carrier protein synthase, a potential regulator of fatty acid biosynthesis in bacteria. J Biol Chem 262(16):7927–7931

    Article  CAS  PubMed  Google Scholar 

  71. Tsay JT, Oh W, Larson TJ, Jackowski S, Rock CO (1992) Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J Biol Chem 267(10):6807–6814

    Article  CAS  PubMed  Google Scholar 

  72. Choi KH, Kremer L, Besra G, Rock CO (2000) Identification and substrate specificity of β-ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J Biol Chem 276(36):28201–28207

    Article  Google Scholar 

  73. Jackowski S (1996) Biosynthesis of pantothenic acid and coenzyme A in Escherichia coli and Salmonella typhimurium: cellular and molecular biology. American Society for Microbiology Press, Washington, DC

    Google Scholar 

  74. Merkel WK, Nichols BP (1996) Characterization and sequence of the Escherichia coli panBCD gene cluster. Microbiol Lett 143:247–252

    Article  CAS  Google Scholar 

  75. Sledz P, Silvestre L, Hung AW, Ciulli A, Blundell TL, Abell C (2010) Optimization of the interligand overhauser effect for fragment linking: application to inhibitor discovery against Mycobacterium tuberculosis pantothenate synthetase. J Am Chem Soc 132:4544–4545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zheng R, Blanchard JS (2001) Steady-state and pre-steadystate kinetic analysis of Mycobacterium tuberculosis pantothenate synthetase. Biochemistry 40:12904–12912

    Article  CAS  PubMed  Google Scholar 

  77. von Delft F, Lewendon A, Dhanaraj V, Blundell TL, Abell C, Smith AG (2001) The crystal structure of E. coli pantothenate synthetase confirms it as a member of the cytidylyltransferase superfamily. Structure 9:439–450

    Article  Google Scholar 

  78. Genschel U, Powell CA, Abell C, Smith AG (1999) The final step of pantothenate biosynthesis in higher plants: cloning and characterization of pantothenate synthetase from Lotus japonicus and Oryza satiVum (rice). Biochem J 341:669–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Espinosa AP, Arjona TR, Rubio MR (2001) Pantothenate synthetase from Fusarium oxysporum f. sp. lycopersici is induced by α-tomatine. Mol Genet Genomics 265(5):922–929

    Article  Google Scholar 

  80. Wang S, Eisenberg D (2003) Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate. Protein Sci 12:1097–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ciulli A, Scott DE, Ando M, Reyes F, Saldanha SA, Tuck KL, Chirgadze DY, Blundell TL, Abell C (2008) Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate. Chembiochem 9(16):2606–2611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tuck KL, Saldanha SA, Birch LM, Smith AG, Abell C (2006) The design and synthesis of inhibitors of pantothenate synthetase. Org Biomol Chem 4(19):3598–3610

    Article  CAS  PubMed  Google Scholar 

  83. Wong D, Chao JD, Av-Gay Y (2013) Mycobacterium tuberculosis-secreted phosphatases: from pathogenesis to targets for TB drug development. Trends Microbiol 21(2):100–109

    Article  CAS  PubMed  Google Scholar 

  84. Zhang ZY (2002) Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development. Annu Rev Pharmacol Toxicol 42(1):209–234

    Article  CAS  PubMed  Google Scholar 

  85. Kennelly PJ, Potts M (1999) Life among the primitives: protein O-phosphatases in prokaryotes. Front Biosci 4:372–385

    Google Scholar 

  86. Shi L, Potts M, Kennelly PJ (1998) The serine, threonine, and/or tyrosine-specific protein kinases and protein phosphatases of prokaryotic organisms: a family portrait. Microbiol Rev 22(4):229–253

    CAS  Google Scholar 

  87. Huyter G, Liu S, Kelly J, Moffat J, Payette P, Kennedy B, Tsaprailis G, Gresse MJ, Ramachandran C (1997) Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. J Biol Chem 272(2):843–851

    Article  Google Scholar 

  88. Tracey AS (2000) Hydroxamido vanadates: aqueous chemistry and function in protein tyrosine phosphatases and cell cultures. J Inorg Biochem 80(1):11–16

    Article  CAS  PubMed  Google Scholar 

  89. Bach H, Sun J, Hmama Z, Av-Gay Y (2006) Mycobacterium avium ssp paratuberculosis PtpA is an endogenous tyrosine phosphatase secreted during infection. Infect Immun 74:6540–6546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Cowley SC, Babakaiff R, Av-Gay Y (2002) Expression and localization of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Res Microbiol 153(4):233–241

    Article  CAS  PubMed  Google Scholar 

  91. Li Y, Strohl WR (1996) Cloning, purification, and properties of a phosphotyrosine protein phosphatase from Streptomyces coelicolor A3 (2). J Bacteriol 178(1):136–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Takayama K, Wang C, Besra GS (2005) Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18:81–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Campbell JW, Cronan JE Jr (2001) Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery. Annu Rev Microbiol 55:305–332

    Article  CAS  PubMed  Google Scholar 

  94. White SW, Zheng J, Zhang YM, Rock CO (2005) The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem 74:791–831

    Article  CAS  PubMed  Google Scholar 

  95. Quemard A, Sacchettini JC, Dessen A, Vilchezes C, Bittman R, Jacobs WR Jr, Blanchard JS (1995) Enzymatic characterization of the target for isoniazid in Mycobaterium tuberculosis. Biochemistry 34:8235–8241

    Article  CAS  PubMed  Google Scholar 

  96. Dessen A, Quemard A, Blanchard JS, Jacobs WR Jr, Sacchettini JC (1995) Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science 267:1638–1641

    Article  CAS  PubMed  Google Scholar 

  97. Wright GD (2012) Back to the future: a new ‘old’ lead for tuberculosis. EMBO Mol Med 4:1029–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, Lisle G, Jacobs WR Jr (1994) InhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263:227–230

    Article  CAS  PubMed  Google Scholar 

  99. Zabinski RF, Blanchard JS (1997) The requirement for manganese and oxygen in the isoniazid-dependent inactivation of Mycobacterium tuberculosis enoyl reductase. J Am Chem Soc 119:2331–2332

    Article  CAS  Google Scholar 

  100. Rozwarski DA, Vilchèze C, Sugantino M, Bittman R, Sacchettini JC (1999) Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate. J Biol Chem 274(22):15582–15589

    Article  CAS  PubMed  Google Scholar 

  101. Musser JM, Kapur V, Williams DL, Kreiswirth BN, Van Soolingen D, Van Embden JD (1996) Characterization of the catalase-peroxidase gene (katG) and inhA locus in isoniazid-resistant and-susceptible strains of Mycobacterium tuberculosis by automated DNA sequencing: restricted array of mutations associated with drug resistance. J Infect Dis 173(1):196–202

    Article  CAS  PubMed  Google Scholar 

  102. McLean KJ, Sabri M, Marshall KR, Lawson RJ, Lewis DG, Clift D, Balding PR, Dunford AJ, Warman AJ, McVey JP, Quin AM, Sutcliffe MJ, Scrutton NS, Munro AW (2005) Biodiversity of cytochrome P450 redox systems. Biochem Soc Trans 33:796–801

    Article  CAS  PubMed  Google Scholar 

  103. Guengerich FP (2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 14(6):611–650

    Article  CAS  PubMed  Google Scholar 

  104. Reichhart DW, Feyereisen R (2000) Cytochromes P450: a success story. Genome Biol 1(6):3001–3009

    Google Scholar 

  105. Quehl P, Hollender J, Schüürmann J, Brossette T, Maas R, Jose J (2016) Co-expression of active human cytochrome P450 1A2 and cytochrome P450 reductase on the cell surface of Escherichia coli. Microb Cell Factories 15(1):26–51

    Article  CAS  Google Scholar 

  106. Munro AW, Lindsay JG (1996) Bacterial cytochromes P-450. Mol Microbiol 20(6):1115–1125

    Article  CAS  PubMed  Google Scholar 

  107. Bentley SD, Chater KF, Cerdeno-Tarraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O’Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3 (2). Nature 417(6885):141–147

    Article  PubMed  Google Scholar 

  108. Notheis C, Drewke C, Leistner E (1997) Purification and characterization of the pyridoxol-5-phosphate:oxygen oxidoreductase (deaminating) from Escherichia coli. Biochim Biophys Acta 1247(2):265–271

    Article  Google Scholar 

  109. Zhao G, Winkler ME (1995) Kinetic limitation and cellular amount of pyridoxine (pyridoxamine) 5′-phosphate oxidase of Escherichia coli K-12. J Bacteriol 177:883–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kwok F, Churchich JE (1980) Interaction between pyridoxal kinase and pyridoxine-5′-P oxidase, two enzymes involved in the metabolism of vitamin B6. J Biol Chem 255:882–887

    Article  CAS  PubMed  Google Scholar 

  111. Salvo M, Yang E, Zhao G, Winkler ME, Schirch V (1998) Expression, purification, and characterization of recombinant Escherichia coli pyridoxine 5′-phosphate oxidase. Protein Expr Purif 13:349–356

    Article  PubMed  Google Scholar 

  112. Pédelacq JD, Rho BS, Kim CY, Waldo GS, Lekin TP, Segelke BW, Rupp B, Hung LW, Kim S, Terwilliger TC (2006) Crystal structure of a putative pyridoxine 5′-phosphate oxidase (Rv2607) from Mycobacterium tuberculosis. Proteins 62(3):563–569

    Article  PubMed  CAS  Google Scholar 

  113. Mashalidis EH, Mukherjee T, Sledz P, Vinkovic DM, Boshoff H, Abell C, Barry CE (2011) Rv2607 from Mycobacterium tuberculosis is a pyridoxine 5’-phosphate oxidase with unusual substrate specificity. PLoS One 6(11):27643–27650

    Article  CAS  Google Scholar 

  114. Sang Y, Barbosa JM, Wu H, Locy RD, Singh NK (2007) Identification of a pyridoxine (pyridoxamine) 5′-phosphate oxidase from Arabidopsis thaliana. FEBS Lett 581(3):344–348

    Article  CAS  PubMed  Google Scholar 

  115. Lehmann HM, Chaffotte A, Pochet S, Labesse G (2001) Thymidylate kinase of Mycobacterium tuberculosis: a chimera sharing properties common to eukaryotic and bacterial enzymes. Protein Sci 10:1195–1205

    Article  Google Scholar 

  116. Sierra IL, Lehmann HM, Gilles AM, Bârzu O, Delarue M (2001) X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 Å resolution. J Mol Biol 311(1):87–100

    Article  CAS  Google Scholar 

  117. Shmalenyuk ER, Kochetkov SN, Alexandrova LA (2013) Novel inhibitors of Mycobacterium tuberculosis growth based on modified pyrimidine nucleosides and their analogues. Russ Chem Rev 82(9):896–915

    Article  CAS  Google Scholar 

  118. Shukla H, Kumar V, Singh AK, Singh N, Kashif M, Siddiqi MI, Krishnan MY, Akhtar MS (2015) Insight into the structural flexibility and function of Mycobacterium tuberculosis isocitrate lyase. Biochimie 110:73–80

    Article  CAS  PubMed  Google Scholar 

  119. Bhusal RP, Bashiri G, Kwai BXC, Sperry J, Leung IKH (2017) Targeting isocitrate lyase for the treatment of latent tuberculosis. Drug Discov Today 22(7):1008–1016

    Article  CAS  PubMed  Google Scholar 

  120. Cheah HL, Lim V, Sandai D (2014) Inhibitors of the Glyoxylate cycle enzime ICL1 in Candida albicans for potential use as antifungal agents. PLoS One 9(4):95951–95959

    Article  CAS  Google Scholar 

  121. Fleischmann RD, Alland D, Eisen JA, Carpenter L, White O, Peterson J, DeBoy R, Dodson R, Gwinn M, Haft D, Hickey E, Kolonay JF, Nelson WC, Umayam LA, Ermolaeva M, Salzberg SL, Delcher A, Utterback T, Weidman J, Khouri H, Gill J, Mikula A, Bishai W, Jacobs WR, Venter JC, Fraser CM (2002) Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains. J Bacteriol 184(19):5479–5490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Bentrup KHZ, Miczak A, Swenson DL, Russell DG (1999) Characterization of activity and expression of Isocitrate Lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol 181(23):7161–7167

    Article  CAS  Google Scholar 

  123. Odell LR, Nilsson MT, Gising J, Lagerlund O, Muthas D, Nordqvist A, Karlen A, Larhed M (2009) Functionalized 3-amino-imidazo [1, 2-α] pyridines: a novel class of drug-like Mycobacterium tuberculosis glutamine synthetase inhibitors. Bioorg Med Chem Lett 19(16):4790–4793

    Article  CAS  PubMed  Google Scholar 

  124. Yuan J, Doucette CD, Fowler WU, Feng XJ, Piazza M, Wingreen HNS, Rabinowitz JD (2009) Metabolomics-driven quantitative analysis of ammonia assimilation in E. coli. Mol Syst Biol 5:302–318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Harth G, Clemens DL, Horwitz MA (1994) Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. Proc Natl Acad Sci U S A 91(20):9342–9346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Tullius MV, Harth G, Horwitz MA (2003) Glutamine synthetase GlnA1 is essential for growth of Mycobacterium tuberculosis in human THP-1 macrophages and Guinea pigs. Infect Immun 71(7):3927–3936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Tullius MV, Harth G, Horwitz MA (2001) High extracellular levels of Mycobacterium tuberculosis glutamine synthetase and superoxide dismutase in actively growing cultures are due to high expression and extracellular stability rather than to a protein-specific export mechanism. Infect Immun 69(10):6348–6363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Herrmann KM, Weaver LM (1999) The shikimate pathway. Annu Rev Plant Biol 50(1):473–503

    Article  CAS  Google Scholar 

  129. Meibom KL, Charbit A (2010) Francisella tularensis metabolism and its relation to virulence. Front Microbiol 1:140–153

    Article  PubMed  PubMed Central  Google Scholar 

  130. Roberts F, Roberts CW, Johnson JJ, Kyle DE, Krell T, Coggins JR, Coombs GH, Milhous WK, Tzipori S, Ferguson DJ, Chakrabarti D, McLeod R (1998) Evidence for the shikimate pathway in apicomplexan parasites. Nature 393(6687):801–805

    Article  CAS  PubMed  Google Scholar 

  131. Ducati RG, Basso LA, Santos DS (2007) Mycobacterial shikimate pathway enzymes as targets for drug design. Curr Drug Targets 8:423–435

    Article  CAS  PubMed  Google Scholar 

  132. Hartmann MD, Bourenkov GP, Oberschall A, Strizhov N, Bartunik HD (2006) Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis. J Mol Biol 364(3):411–423

    Article  CAS  PubMed  Google Scholar 

  133. Pallen MJ (2002) The ESAT-6/WXG100 superfamily – and a new Grampositive secretion system? Trends Microbiol 10:209–212

    Article  CAS  PubMed  Google Scholar 

  134. Brodin P, Jonge MI, Majlessi L, Leclerc C, Nilges M, Cole ST, Brosch R (2005) Functional analysis of early secreted antigenic target-6, the dominant T-cell antigen of Mycobacterium tuberculosis, reveals key residues involved in secretion, complex formation, virulence, and immunogenicity. J Biol Chem 280(40):33953–33959

    Article  CAS  PubMed  Google Scholar 

  135. Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA, Gordon SV, Hewinson RG, Burke B, Norman J, Williamson RA, Carr MD (2005) Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. EMBO J 24:2491–2498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE, Lewinsohn DM, Smith S, Sherman DR (2004) Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol Micobiol 51(2):359–370

    Article  CAS  Google Scholar 

  137. Renshaw PS, Veverka V, Kelly G, Frenkiel TA, Williamson RA, Gordon SV, Hewinson RG, Carr MD (2004) Letter to the editor: Sequence-specific assignment and secondary structure determination of the 195-residue complex formed by the Mycobacterium tuberculosis proteins CFP-10 and ESAT-6. J Biomol NMR 30:225–226

    Article  CAS  PubMed  Google Scholar 

  138. Meher AK, Bal NC, Chary KV, Arora A (2006) Mycobacterium tuberculosis H37Rv ESAT-6-CFP-10 complex formation confers thermodynamic and biochemical stability. FEBS J 273(7):1445–1462

    Article  CAS  PubMed  Google Scholar 

  139. Berthet FX, Rasmussen PB, Rosenkrands I, Andersen P, Gicquel B (1998) A Mycobacterium tuberculosis operon encoding ESAT6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology 144(11):3195–3203

    Article  CAS  PubMed  Google Scholar 

  140. Wards BJ, De Lisle GW, Collins DM (2000) An ESAT-6 knockout mutant of Mycobacterium bovis produced by homologous recombination will contribute to the development of a live tuberculosis vaccine. Tuber Lung Dis 80(5):185–189

    Article  CAS  PubMed  Google Scholar 

  141. Nollmann M, Crisona NJ, Arimondo PB (2007) Thirty years of Escherichia coli DNA gyrase: from in vivo function to single molecule mechanism. Biochimie 89:490–499

    Article  PubMed  CAS  Google Scholar 

  142. Bates AD, Maxwell A (2007) Energy coupling in type II topoisomerases: why do they hydrolyze ATP? Biochemistry 46:7929–7941

    Article  CAS  PubMed  Google Scholar 

  143. Stanger FV, Dehio C, Schirmer T (2014) Structure of the N-terminal Gyrase B fragment in complex with ADPPi reveals rigid-body motion induced by ATP hydrolysis. PLoS One 9(9):107289–107302

    Article  CAS  Google Scholar 

  144. Champoux JJ (2001) DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 70:369–413

    Article  CAS  PubMed  Google Scholar 

  145. Chopra S, Matsuyama K, Tran T, Malerich JP, Wan B, Franzblau SG, Lun S, Guo H, Maiga MC, Bishai WR, Madrid PB (2012) Evaluation of gyrase B as a drug target in Mycobacterium tuberculosis. J Antimicrob Chemother 67(2):415–421

    Article  CAS  PubMed  Google Scholar 

  146. Mugumbate G, Abrahams KA, Cox JAG, Papadatos G, Westen G, Lelièvre J, Calus ST, Loman NJ, Ballell L, Barros D, Overington JP, Besra GS (2015) Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation. PLoS One 10(2):121492

    Google Scholar 

  147. Feng J, Goswami S, Howell EE (2008) R67, the other dihydrofolate reductase: rational design of an alternate active site configuration. Biochemistry 47:555–565

    Article  CAS  PubMed  Google Scholar 

  148. Argyrou A, Vetting MW, Aladegbami B, Blanchard JS (2006) Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid. Nat Struct Mol Biol 13:408–413

    Article  CAS  PubMed  Google Scholar 

  149. El-Subbagh HI, Hassan GS, El-Messery SM, Al-Rashood ST, Al-Omary FA, Abulfadl YS, Shabayek MI (2014) Nonclassical antifolates: part 5. Benzodiazepine analogs as a new class of DHFR inhibitors: synthesis, antitumor testing and molecular modeling study. Eur J Med Chem 74:234–245

    Article  CAS  PubMed  Google Scholar 

  150. Li R, Sirawaraporn R, Chitnumsub P, Sirawaraporn W, Wooden J, Athappilly F, Turley S, Hol WG (2000) Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opprtunities for the design of novel tuberculosis drugs. J Mol Biol 295:307–323

    Article  CAS  PubMed  Google Scholar 

  151. Cody V, Galitsky N, Luft JR, Pangborn W, Rosowsky A, Blakley RL (1997) Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight binding inhibitor PT523. Biochemistry 36:4399–4411

    Article  Google Scholar 

  152. White EL, Ross LJ, Cunningham A, Escuyer V (2004) Cloning, expression and characterization of Mycobacterium tuberculosis dihydrofolate reductase. FEMS Microbiol Lett 232:101–105

    Article  CAS  PubMed  Google Scholar 

  153. Sardarian A, Douglas KT, Read M, Sims PFG, Hyde JE, Chitnumsub P, Sirawaraporn R, Sirawaraporn W (2003) Pyrimethamine analogues as strong inhibitors of double and quadruple mutants of dihydrofolate reductase in human malaria parasites. Org Biomol Chem 1:960–964

    Article  CAS  PubMed  Google Scholar 

  154. Morphy JR (2012) The challenges of multi-target lead optimization. In: Morphy JR, Harris CJ (eds) Designing multi-target drugs. The Royal Society of Chemistry, London

    Chapter  Google Scholar 

  155. Abdolmaleki A, Ghasemi JB, Ghasemi F (2017) Computer aided drug design for multi-target drug design: SAR/QSAR, molecular docking and pharmacophore methods. Curr Drug Targets 18(5):556–575

    Article  CAS  PubMed  Google Scholar 

  156. Mohareb RM, El-Sayed NNE, Abdelaziz MA (2013) The knoevenagel reactions of pregnenolone with cyanomethylene reagents: synthesis of thiophene, thieno[2,3-b]pyridine, thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines. Steroids 78:1209–1219

    Article  CAS  PubMed  Google Scholar 

  157. Meotti FC, Silva DO, Santos ARS, Zeni G, Rocha JBT, Nogueira CW (2003) Thiophenes and furans derivatives: a new class of potential pharmacological agents. Environ Toxicol Pharmacol 15(1):37–44

    Article  CAS  PubMed  Google Scholar 

  158. Ferreira AP, da Silva JLF, Duarte MT, da Piedade MFM, Robalo MP, Harjivan SG, Marzano C, Gandin V, Marques MM (2009) Synthesis and characterization of new organometallic benzo[b]thiophene derivatives with potential antitumor properties. Organometallics 28(18):5412–5423

    Article  CAS  Google Scholar 

  159. Khalil AM, Berghot MA, Gouda MA (2009) Synthesis and antibacterial activity of some new thiazole and thiophene derivatives. Eur J Med Chem 44(11):4434–4440

    Article  CAS  PubMed  Google Scholar 

  160. Lu X, Wan B, Franzblau SG, You Q (2011) Design, synthesis and anti-tubercular evaluation of new 2-acylated and 2-alkylated amino-5-(4-(benzyloxy) phenyl) thiophene-3-carboxylic acid derivatives. Part 1. Eur J Med Chem 46(9):3551–3563

    Article  CAS  PubMed  Google Scholar 

  161. Wilson R, Kumar P, Parashar V, Vilchèze C, Veyron-Churlet R, Freundlich JS, Barnes SW, Walker JR, Szymonifka J, Marchiano E, Shenai S, Colangeli R, Jacobs WR, Neiditch MB, Kremer L, Alland D (2013) Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis. Nat Chem Biol 9(8):499–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Mahajan PS, Nikam MD, Nawale LU, Khedkar VM, Sarkar D, Gill CH (2016) Synthesis and antitubercular activity of new benzo[b]thiophenes. ACS Med Chem Lett 7:751–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Leitans J, Sprudza A, Tanc M, Vozny I, Zalubovskis R, Tars K, Supuran CT (2013) 5-Substituted-(1, 2, 3-triazol-4-yl) thiophene-2-sulfonamides strongly inhibit human carbonic anhydrases I, II, IX and XII: solution and X-ray crystallographic studies. Bioorg Med Chem 21(17):5130–5138

    Article  CAS  PubMed  Google Scholar 

  164. Wang ZC, Qin YJ, Wang PF, Yang YA, Wen Q, Zhang X, Qiu HY, Duan YT, Wang YT, Sang YL, Zhu HL (2013) Sulfonamides containing coumarin moieties selectively and potently inhibit carbonic anhydrases II and IX: design, synthesis, inhibitory activity and 3D-QSAR analysis. Eur J Med Chem 66:1–11

    Article  CAS  PubMed  Google Scholar 

  165. Supuran CT, Casini A, Scozzafava A (2003) Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents. Med Res Rev 5:535–558

    Article  CAS  Google Scholar 

  166. Scozzafava A (2003) Anticancer and antiviral sulfonamides. Curr Med Chem 10:925–953

    Article  CAS  PubMed  Google Scholar 

  167. Özbek N, Katırcıoglu H, Karacan N, Baykal T (2007) Synthesis, characterization and antimicrobial activity of new aliphatic sulfonamide. Bioorg Med Chem 15(15):5105–5109

    Article  PubMed  CAS  Google Scholar 

  168. Naidu KM, Nagesh HN, Singh M, Sriram D, Yogeeswari P, Sekhar KVGC (2015) Novel amide and sulfonamide derivatives of 6-(piperazin-1-yl) phenanthridine as potent Mycobacterium tuberculosis H37Rv inhibitors. Eur J Med Chem 92:415–426

    Article  CAS  PubMed  Google Scholar 

  169. Oliveira KN, Chiaradia LD, Martins PGA, Mascarello A, Cordeiro MNS, Guido RVC, Andricopulo AD, Yunes RA, Nunes RJ, Vernal J, Terenzi H (2011) Sulfonyl-hydrazones of cyclic imides derivatives as potent inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase B (PtpB). MedChemComm 2(6):500–504

    Article  CAS  Google Scholar 

  170. Elias DW, Beazely MA, Kandepu NM (1999) Bioactivities of chalcones. Curr Med Chem 6(12):1125

    Article  PubMed  Google Scholar 

  171. Aoki N, Muko M, Ohta E, Ohta S (2008) C-geranylated chalcones from the stems of Angelica keiskei with superoxide-scavenging activity. J Nat Prod 71(7):1308–1310

    Article  CAS  PubMed  Google Scholar 

  172. Mascarello A, Chiaradia LD, Vernal J, Villarino A, Guido RV, Perizzolo P, Poirier V, Wong D, Martins PGA, Nunes RJ, Yunes RA, Andricupulo AD, Gay YA, Terenzi H (2010) Inhibition of Mycobacterium tuberculosis tyrosine phosphatase PtpA by synthetic chalcones: kinetics, molecular modeling, toxicity and effect on growth. Bioorg Med Chem 18(11):3783–3789

    Article  CAS  PubMed  Google Scholar 

  173. Yadav DK, Ahmad I, Shukla A, Khan F, Negi AS, Gupta A (2014) QSAR and docking studies on chalcone derivatives for antitubercular activity against M. tuberculosis H37Rv. J Chemom 28(6):499–507

    Article  CAS  Google Scholar 

  174. Gond DS, Meshram RJ, Jadhav SG, Wadhwa G, Gacche RN (2013) In silico screening of chalcone derivatives as potential inhibitors of dihydrofolate reductase: assessment using molecular docking, paired potential and molecular hydrophobic potential studies. Drug Invent Today 5(3):182–191

    Article  CAS  Google Scholar 

  175. Carroll MW, Jeon D, Mountz JM, Lee JD, Jeong YJ, Zia N, Lee M, Lee J, Via LE, Lee S, Eum SY, Lee SJ, Goldfeder LC, Cai Y, Jin B, Kim Y, Oh T, Chen RY, Dodd LE, Gu W, Dartois V, Park SK, Kim CT, Barry CE III, Cho SN (2013) Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis. Antimicrob Agents Chemother 57:3903–3909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Mukherjee T, Boshoff H (2011) Nitroimidazoles for the treatment of TB: past, present and future. Future Med Chem 3:1427–1454

    Article  CAS  PubMed  Google Scholar 

  177. Sharma A, Subbias KK, Robine O, Chaturvedi I, Nigam A, Sharma N, Chaudhary PP (2012) Computational finding of potential inhibitor for cytochrome P450 mono-oxygenases enzyme of Mycobacterium tuberculosis. Bioinformation 8(19):931

    Article  PubMed  PubMed Central  Google Scholar 

  178. Gupta N, Vyas VK, Patel BD, Ghate M (2017) Design of 2-nitroimidazooxazine derivatives as deazaflavin-dependent nitroreductase (Ddn) activators as anti-mycobacterial agents based on 3D QSAR, HQSAR, and docking study with in silico prediction of activity and toxicity. Comput Life Sci 1–15

    Google Scholar 

  179. Somasundaram S, Anand RS, Venkatesan P, Paramasivan CN (2013) Bactericidal activity of PA-824 against Mycobacterium tuberculosis under anaerobic conditions and computational analysis of its novel analogues against mutant Ddn receptor. BMC Microbiol 13(1):218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Kumar SM, Jaleel UCA (2016) Molecular docking studies of PA-824 with pyridoxine 5′-phosphate oxidase. Biol Med 8(2):1–4

    Google Scholar 

  181. Keri RS, Hiremathad A, Budagumpi S, Nagaraja BM (2015) Comprehensive review in current developments of benzimidazole-based medicinal chemistry. Chem Biol Drug Des 86(1):19–65

    Article  PubMed  CAS  Google Scholar 

  182. Grassi A, Ippen J, Bruno M, Thomas G (1991) BAY P 1455, a thiazolylaminobenzimidazole derivative with gastroprotective properties in the rat. Eur J Pharmacol 195(2):251–259

    Article  CAS  PubMed  Google Scholar 

  183. Saleshier FM, Divakar MC (2011) Design, docking and synthesis of some 6-benzimidazoyl pyrans and screening of their anti tubercular activity. Eur J Exp Biol 1(2):150–159

    CAS  Google Scholar 

  184. Soni V, Suryadevara P, Sriram D, Kumar S, Nandicoori VK, Yogeeswari P, OSDD Consortium (2015) Structure-based design of diverse inhibitors of Mycobacterium tuberculosis N-acetylglucosamine-1-phosphate uridyltransferase: combined molecular docking, dynamic simulation, and biological activity. J Mol Model 21(7):174

    Article  PubMed  CAS  Google Scholar 

  185. Priyadarsini R, Tharani CB, Niraimathi V (2012) Docking, synthesis, characterisation of certain substituted benzimidazole pyrimidines as potent DHFR inhibitors with antimycobacterial activity. J Pharm Res 5(11):5173–5177

    CAS  Google Scholar 

  186. Aanandhi MV, Chandran M, Sujatha R, Nishanthi M, Vijayakumar B (2012) Comparative study on conventional and microwave assisted synthesis and molecular docking studies of mannich bases of benzimidazoles and their derivatives. Int J Biol Pharm Res 3(4):1–9

    Google Scholar 

  187. Anguru MR, Taduri AK, Bhoomireddy RD, Jojula M, Gunda SK (2017) Novel drug targets for Mycobacterium tuberculosis: 2-heterostyrylbenzimidazoles as inhibitors of cell wall protein synthesis. Chem Central J 11(1):68

    Article  CAS  Google Scholar 

  188. Otvos L (2008) Peptide-based drug design: here and now. Methods Mol Biol 494:1–8

    Article  CAS  PubMed  Google Scholar 

  189. Hancock R, Bertrand HC, Tsujita T, Naz S, El-Bakry A, Laoruchupong J, Hayes JD, Wells G (2012) Peptide inhibitors of the Keap1-Nrf2 protein-protein interaction. Free Radic Biol Med 52:444–451

    Article  CAS  PubMed  Google Scholar 

  190. Shi W, Ma H, Duan Y, Aubart K, Fang Y, Zonis R, Yang L, Hu W (2011) Design, synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives as novel peptide deformylase inhibitors. Bioorg Med Chem Lett 21:1060–1063

    Article  CAS  PubMed  Google Scholar 

  191. Kumar M, Vijayakrishnan R, Rao GS (2010) In silico structure-based design of a novel class of potent and selective small peptide inhibitor of Mycobacterium tuberculosis dihydrofolate reductase, a potential target for anti-TB drug discovery. Mol Divers 14(3):595–604

    Article  CAS  PubMed  Google Scholar 

  192. Chandra K, Dutta D, Das AK, Basak A (2010) Design, synthesis and inhibition activity of novel cyclic peptides against protein tyrosine phosphatase A from Mycobacterium tuberculosis. Bioorg Med Chem 18(23):8365–8373

    Article  CAS  PubMed  Google Scholar 

  193. Yang Y, Gao P, Liu Y, Ji X, Gan M, Guan Y, Hao X, Li Z, Xiao C (2011) A discovery of novel Mycobacterium tuberculosis pantothenate synthetase inhibitors based on the molecular mechanism of actinomycin D inhibition. Bioorg Med Chem Lett 21(13):3943–3946

    Article  CAS  PubMed  Google Scholar 

  194. Kumar M, Sharma S, Srinivasan A, Singh TP, Kaur P (2011) Structure-based in silico rational design of a selective peptide inhibitor for thymidine monophosphate kinase of Mycobacterium tuberculosis. J Mol Model 17(5):1173–1182

    Article  CAS  PubMed  Google Scholar 

  195. Liu X, Zang Y, Sun B, Yin Y (2014) Optimization of phage heptapeptide library-screening process for developing inhibitors of the isocitrate lyase homologue from Mycobacterium tuberculosis. Med Chem Res 23(5):2543–2553

    Article  CAS  Google Scholar 

  196. Perumal P, Pandey VP, Parasuraman P (2014) Docking studies on antimicrobial peptides related to apidaecinia and human histatin against glutamine synthetase and RNA polymerase in Mycobacterium tuberculosis. Asian J Pharm Clin Res 7(5):195–201

    Google Scholar 

  197. Kumar M, Verma S, Sharma S, Srinivasan A, Singh TP, Kaur P (2010) Structure-based In silico design of a high-affinity dipeptide inhibitor for novel protein drug target shikimate kinase of Mycobacterium tuberculosis. Chem Biol Drug Des 76(3):277–284

    CAS  PubMed  Google Scholar 

  198. Gavrish E, Sit CS, Cao S, Kandror O, Spoering A, Peoples A, Ling L, Fetterman A, Hughes D, Bissel A, Torrey H, Akopian T, Mueller A, Epstein S, Goldberg A, Clardy J, Lewis K (2014) Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chem Biol 21(4):509–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Hu W, Lin JP, Song LR, Long YQ (2015) Direct synthesis of 2-aryl-4-quinolones via transition-metal-free intramolecular oxidative C (sp3)-H/C(sp3)-H coupling. Org Lett 17:1268–1271

    Article  CAS  PubMed  Google Scholar 

  200. Mitscher LA (2005) Bacterial topoisomerase inhibitors: quinolone and pyridone antibacterial agents. Chem Rev 105:559–592

    Article  CAS  PubMed  Google Scholar 

  201. Guo X, Liu ML, Guo HY, Wang YC, Wang JX (2011) Synthesis and in vitro antibacterial activity of 7-(3-amino-6,7-dihydro-2-methyl-2H-pyrazolo[4,3-c]pyridin-5(4H)-yl) fluoroquinolone derivatives. Molecules 16:2626–2635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Aldred KJ, Kerns RJ, Osheroff N (2014) Mechanism of quinolone action and resistance. Biochemistry 53:1565–1574

    Article  CAS  PubMed  Google Scholar 

  203. Guzman JD, Wube A, Evangelopoulos D, Gupta A, Hüfner A, Basavannacharya C, Rahman M, Thomaschitz C, Bauer R, McHugh TD, Nobeli I, Prieto JM, Gibbons S, Bucar F, Bhakta S (2011) Interaction of N-methyl-2-alkenyl-4-quinolones with ATP-dependent MurE ligase of Mycobacterium tuberculosis: antibacterial activity, molecular docking and inhibition kinetics. J Antimicrob Chemother 66(8):1766–1772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Cunha EF, Barbosa EF, Oliveira AA, Ramalho TC (2010) Molecular modeling of Mycobacterium tuberculosis DNA gyrase and its molecular docking study with gatifloxacin inhibitors. J Biomol Struct Dyn 27(5):619–625

    Article  PubMed  Google Scholar 

  205. Maddela S, Makula A (2016) Design, synthesis and docking study of some novel isatin-quinoline hybrids as potential antitubercular agents. Anti-Infect Agents 14(1):53–62

    Article  CAS  Google Scholar 

  206. Minovski N, Perdih A, Solmajer T (2012) Combinatorially-generated library of 6-fluoroquinolone analogs as potential novel antitubercular agents: a chemometric and molecular modeling assessment. J Mol Model 18(5):1735–1753

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Federal University of Paraíba, Health Center, João Pessoa, PB, Brazil

    Jéssika de Oliveira Viana & Marcus T. Scotti

  2. Federal University of Paraíba, Health Center, Teaching and Research Management - University Hospital, João Pessoa, PB, Brazil

    Luciana Scotti

Authors
  1. Jéssika de Oliveira Viana
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  2. Marcus T. Scotti
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  3. Luciana Scotti
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Corresponding author

Correspondence to Luciana Scotti .

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Editors and Affiliations

  1. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India

    Kunal Roy

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de Oliveira Viana, J., Scotti, M.T., Scotti, L. (2018). Molecular Docking Studies in Multitarget Antitubercular Drug Discovery. In: Roy, K. (eds) Multi-Target Drug Design Using Chem-Bioinformatic Approaches. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/7653_2018_28

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  • DOI: https://doi.org/10.1007/7653_2018_28

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8732-0

  • Online ISBN: 978-1-4939-8733-7

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