14. Mikusova K, Slayden RA, Besra GS, Brennan PJ (1995) Biogenesis of the mycobacterial
cell wall and the site of action of ethambutol. Antimicrob Agents Chemother 39:2484–2489
15. Richter A, Rudolph I, Möllmann U, Voigt K, Chung C-W, Singh OM, Rees M,
Mendoza-Losana A, Bates R, Ballell L (2018) Novel insight into the reaction of nitro,
nitroso and hydroxylamino benzothiazinones and of benzoxacinones with Mycobacterium
tuberculosis DprE1. Sci Rep 8:13473
16. Gao P, Yang Y, Xiao C, Liu Y, Gan M, Guan Y, Hao X, Meng J, Zhou S, Chen X (2012)
Identification and validation of a novel lead compound targeting 4-diphosphocytidyl2-C-methylerythritol synthetase (IspD) of mycobacteria. Eur J Pharmacol 694:45–52
17. Kantardjieff KA, Kim C-Y, Naranjo C, Waldo GS, Lekin T, Segelke BW, Zemla A,
Park MS, Terwilliger TC, Rupp B (2004) Mycobacterium tuberculosis RmlC epimerase
(Rv3465): a promising drug-target structure in the rhamnose pathway. Acta Crystallogr D
Biol Crystallogr 60:895–902
18. Björkelid C, Bergfors T, Henriksson LM, Stern AL, Unge T, Mowbray SL, Jones TA (2011)
Structural and functional studies of mycobacterial IspD enzymes. Acta Crystallogr D Biol
Crystallogr 67:403–414
19. DeBarber AE, Mdluli K, Bosman M, Bekker L-G, Barry CE (2000) Ethionamide activation
and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci
97:9677–9682
20. Johnsson K, King DS, Schultz PG (1995) Studies on the mechanism of action of isoniazid
and ethionamide in the chemotherapy of tuberculosis. J Am Chem Soc 117:5009–5010
21. Manjunatha UH, Rao SP, Kondreddi RR, Noble CG, Camacho LR, Tan BH, Ng SH, Ng PS,
Ma NL, Lakshminarayana SB (2015) Direct inhibitors of InhA are active against
Mycobacterium tuberculosis. Sci Transl Med 7:269ra3
22. Pan P, Tonge JP (2012) Targeting InhA, the FASII enoyl-ACP reductase: SAR studies on
novel inhibitor scaffolds. Curr Topics Med Chem 12:672–693
23. Šink R, Sosič I, Živec M, Fernandez-Menendez R, Turk S, Pajk S, Alvarez-Gomez D,
Lopez-Roman EM, Gonzales-Cortez C, Rullas-Triconado J (2014) Design, synthesis, and
evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase
(InhA) for the treatment of tuberculosis. J Med Chem 58:613–624
24. Martínez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Álvarez-Gómez D, Alvarez E,
Ferrer-Bazaga S, García-Pérez A, Ortega F, Angulo-Barturen I (2016) Antitubercular drugs
for an old target: GSK693 as a promising InhA direct inhibitor. EBioMedicine 8:291–301
25. Barkan D, Liu Z, Sacchettini JC, Glickman MS (2009) Mycolic acid cyclopropanation is
essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis.
Chem Biol 16:499–509
26. Wilson R, Kumar P, Parashar V, Vilchèze C, Veyron-Churlet R, Freundlich JS, Barnes SW,
Walker JR, Szymonifka MJ, Marchiano E (2013) Antituberculosis thiophenes define a
requirement for Pks13 in mycolic acid biosynthesis. Nat Chem Biol 9:499–506
27. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, Fischer E, Barnes SW, Walker JR,
Alland D, Barry CE (2012) 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 (AAC) 05708-11
28. Ronning DR, Klabunde T, Besra GS, Vissa VD, Belisle JT, Sacchettini JC (2000) Crystal
structure of the secreted form of antigen 85C reveals potential targets for mycobacterial
drugs and vaccines. Nat Struct Mol Biol 7:141–146
29. Warrier T, Tropis M, Werngren J, Diehl A, Gengenbacher M, Schlegel B, Schade M,
Oschkinat H, Daffe M, Hoffner S (2012) Antigen 85C inhibition restricts Mycobacterium
tuberculosis growth through disruption of cord factor biosynthesis. Antimicrob Agents
Chemother 1735–1743
30. Kovač A, Wilson RA, Besra GS, Filipič M, Kikelj D, Gobec S (2006) New lipophilic
phthalimido-and 3-phenoxybenzyl sulfonates: inhibition of antigen 85C mycolyltransferase
activity and cytotoxicity. J Enzyme Inhib Med Chem 21:391–397
338
A. C. Pushkaran et al.
cell wall and the site of action of ethambutol. Antimicrob Agents Chemother 39:2484–2489
15. Richter A, Rudolph I, Möllmann U, Voigt K, Chung C-W, Singh OM, Rees M,
Mendoza-Losana A, Bates R, Ballell L (2018) Novel insight into the reaction of nitro,
nitroso and hydroxylamino benzothiazinones and of benzoxacinones with Mycobacterium
tuberculosis DprE1. Sci Rep 8:13473
16. Gao P, Yang Y, Xiao C, Liu Y, Gan M, Guan Y, Hao X, Meng J, Zhou S, Chen X (2012)
Identification and validation of a novel lead compound targeting 4-diphosphocytidyl2-C-methylerythritol synthetase (IspD) of mycobacteria. Eur J Pharmacol 694:45–52
17. Kantardjieff KA, Kim C-Y, Naranjo C, Waldo GS, Lekin T, Segelke BW, Zemla A,
Park MS, Terwilliger TC, Rupp B (2004) Mycobacterium tuberculosis RmlC epimerase
(Rv3465): a promising drug-target structure in the rhamnose pathway. Acta Crystallogr D
Biol Crystallogr 60:895–902
18. Björkelid C, Bergfors T, Henriksson LM, Stern AL, Unge T, Mowbray SL, Jones TA (2011)
Structural and functional studies of mycobacterial IspD enzymes. Acta Crystallogr D Biol
Crystallogr 67:403–414
19. DeBarber AE, Mdluli K, Bosman M, Bekker L-G, Barry CE (2000) Ethionamide activation
and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci
97:9677–9682
20. Johnsson K, King DS, Schultz PG (1995) Studies on the mechanism of action of isoniazid
and ethionamide in the chemotherapy of tuberculosis. J Am Chem Soc 117:5009–5010
21. Manjunatha UH, Rao SP, Kondreddi RR, Noble CG, Camacho LR, Tan BH, Ng SH, Ng PS,
Ma NL, Lakshminarayana SB (2015) Direct inhibitors of InhA are active against
Mycobacterium tuberculosis. Sci Transl Med 7:269ra3
22. Pan P, Tonge JP (2012) Targeting InhA, the FASII enoyl-ACP reductase: SAR studies on
novel inhibitor scaffolds. Curr Topics Med Chem 12:672–693
23. Šink R, Sosič I, Živec M, Fernandez-Menendez R, Turk S, Pajk S, Alvarez-Gomez D,
Lopez-Roman EM, Gonzales-Cortez C, Rullas-Triconado J (2014) Design, synthesis, and
evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase
(InhA) for the treatment of tuberculosis. J Med Chem 58:613–624
24. Martínez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Álvarez-Gómez D, Alvarez E,
Ferrer-Bazaga S, García-Pérez A, Ortega F, Angulo-Barturen I (2016) Antitubercular drugs
for an old target: GSK693 as a promising InhA direct inhibitor. EBioMedicine 8:291–301
25. Barkan D, Liu Z, Sacchettini JC, Glickman MS (2009) Mycolic acid cyclopropanation is
essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis.
Chem Biol 16:499–509
26. Wilson R, Kumar P, Parashar V, Vilchèze C, Veyron-Churlet R, Freundlich JS, Barnes SW,
Walker JR, Szymonifka MJ, Marchiano E (2013) Antituberculosis thiophenes define a
requirement for Pks13 in mycolic acid biosynthesis. Nat Chem Biol 9:499–506
27. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, Fischer E, Barnes SW, Walker JR,
Alland D, Barry CE (2012) 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 (AAC) 05708-11
28. Ronning DR, Klabunde T, Besra GS, Vissa VD, Belisle JT, Sacchettini JC (2000) Crystal
structure of the secreted form of antigen 85C reveals potential targets for mycobacterial
drugs and vaccines. Nat Struct Mol Biol 7:141–146
29. Warrier T, Tropis M, Werngren J, Diehl A, Gengenbacher M, Schlegel B, Schade M,
Oschkinat H, Daffe M, Hoffner S (2012) Antigen 85C inhibition restricts Mycobacterium
tuberculosis growth through disruption of cord factor biosynthesis. Antimicrob Agents
Chemother 1735–1743
30. Kovač A, Wilson RA, Besra GS, Filipič M, Kikelj D, Gobec S (2006) New lipophilic
phthalimido-and 3-phenoxybenzyl sulfonates: inhibition of antigen 85C mycolyltransferase
activity and cytotoxicity. J Enzyme Inhib Med Chem 21:391–397
338
A. C. Pushkaran et al.