Novel small molecule inhibitors of MDR mycobacterium tuberculosis by NMR fragment screening of antigen 85C

Journal of Medicinal Chemistry

Volumn 53, Issue 23, 2010, Pages 8362-8367

  Scheich, Christoph ^b   Puetter, Vera ^c   Schade, Markus ^a,d  

^a MerLion Pharmaceuticals GmbH   (Germany)

^b EVOTEC AG   (Germany)

^c BAYER PHARMA AG   (Germany)

^d PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; ANTIGEN 85 C; LIGAND; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; CELL SCREENING; CHEMOTHERAPY; CLINICAL ARTICLE; CLINICAL TRIAL; GENOME; HUMAN; MULTIDRUG RESISTANT TUBERCULOSIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE;

ACYLTRANSFERASES; ANTIGENS, BACTERIAL; ANTITUBERCULAR AGENTS; CATALYTIC DOMAIN; DRUG RESISTANCE, MICROBIAL; DRUG RESISTANCE, MULTIPLE; MYCOBACTERIUM TUBERCULOSIS; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR;

EID: 78649858286     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100993z     Document Type: Article

References (25)

1. Zhang, Y.; Post-Martens, K.; Denkin, S. New drug candidates and therapeutic targets for tuberculosis therapy Drug Discovery Today 2006, 11, 21-27
2. Payne, D. J.; Gwynn, M. N.; Holmes, D. J.; Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery Nat. Rev. Drug Discovery 2007, 6, 29-40
3. Young, D. B.; Perkins, M. D.; Duncan, K.; Barry, C. E., 3rd. Confronting the scientific obstacles to global control of tuberculosis J. Clin. Invest. 2008, 118, 1255-1265
4. Kremer, L.; Dover, L. G.; Carrere, S.; Nampoothiri, K. M.; Lesjean, S.; Brown, A. K.; Brennan, P. J.; Minnikin, D. E.; Locht, C.; Besra, G. S. Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis Biochem. J. 2002, 364, 423-430
5. Brennan, P. J.; Nikaido, H. The envelope of mycobacteria Annu. Rev. Biochem. 1995, 64, 29-63
6. Belisle, J. T.; Vissa, V. D.; Sievert, T.; Takayama, K.; Brennan, P. J.; Besra, G. S. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis Science 1997, 276, 1420-1422
7. Anderson, D. H.; Harth, G.; Horwitz, M. A.; Eisenberg, D. An interfacial mechanism and a class of inhibitors inferred from two crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory protein (antigen 85B), a mycolyl transferase J. Mol. Biol. 2001, 307, 671-681
8. Ronning, D. R.; Vissa, V.; Besra, G. S.; Belisle, J. T.; Sacchettini, J. C. Mycobacterium tuberculosis antigen 85A and 85C structures confirm binding orientation and conserved substrate specificity J. Biol. Chem. 2004, 279, 36771-36777
9. Jackson, M.; Raynaud, C.; Laneelle, M. A.; Guilhot, C.; Laurent-Winter, C.; Ensergueix, D.; Gicquel, B.; Daffe, M. Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope Mol. Microbiol. 1999, 31, 1573-1587
10. Schade, M. NMR fragment screening: advantages and applications IDrugs 2006, 9, 110-113
11. Hajduk, P. J.; Greer, J. A decade of fragment-based drug design: strategic advances and lessons learned Nat. Rev. Drug Discovery 2007, 6, 211-219
12. Abad-Zapatero, C.; Metz, J. T. Ligand efficiency indices as guideposts for drug discovery Drug Discovery Today 2005, 10, 464-469
13. Shandil, R. K.; Jayaram, R.; Kaur, P.; Gaonkar, S.; Suresh, B. L.; Mahesh, B. N.; Jayashree, R.; Nandi, V.; Bharath, S.; Balasubramanian, V. Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis: evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy Antimicrob. Agents Chemother. 2007, 51, 576-582
14. Sanki, A. K.; Boucau, J.; Srivastava, P.; Adams, S. S.; Ronning, D. R.; Sucheck, S. J. Synthesis of methyl 5- S -alkyl-5-thio- d -arabinofuranosides and evaluation of their antimycobacterial activity Bioorg. Med. Chem. 2008, 16, 5672-5682
15. Hajduk, P. J. Fragment-based drug design: how big is too big? J. Med. Chem. 2006, 49, 6972-6976
16. Harth, G.; Horwitz, M. A.; Tabatadze, D.; Zamecnik, P. C. Targeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: proof of principle by using antisense technology Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15614-15619
17. Rose, J. D.; Maddry, J. A.; Comber, R. N.; Suling, W. J.; Wilson, L. N.; Reynolds, R. C. Synthesis and biological evaluation of trehalose analogs as potential inhibitors of mycobacterial cell wall biosynthesis Carbohydr. Res. 2002, 337, 105-120
18. Gobec, S.; Plantan, I.; Mravljak, J.; Svajger, U.; Wilson, R. A.; Besra, G. S.; Soares, S. L.; Appelberg, R.; Kikelj, D. Design, synthesis, biochemical evaluation and antimycobacterial action of phosphonate inhibitors of antigen 85C, a crucial enzyme involved in biosynthesis of the mycobacterial cell wall Eur. J. Med. Chem. 2007, 42, 54-63
19. Kovac, A.; Wilson, R. A.; Besra, G. S.; Filipic, M.; Kikelj, D.; Gobec, S. New lipophilic phthalimido- and 3-phenoxybenzyl sulfonates: inhibition of antigen 85C mycolyltransferase activity and cytotoxicity J. Enzyme Inhib. Med. Chem. 2006, 21, 391-397
20. Protopopova, M.; Hanrahan, C.; Nikonenko, B.; Samala, R.; Chen, P.; Gearhart, J.; Einck, L.; Nacy, C. A. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines J. Antimicrob. Chemother. 2005, 56, 968-974
21. Matsumoto, M.; Hashizume, H.; Tomishige, T.; Kawasaki, M.; Tsubouchi, H.; Sasaki, H.; Shimokawa, Y.; Komatsu, M. OPC-67683, a nitro-dihydro- imidazooxazole derivative with promising action against tuberculosis in vitro and in mice PLoS Med. 2006, 3, 2131-2144
22. Sridhar, M.; Rao, R. M.; Baba, N. H. K.; Kumbhare, R. M. Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes Tetrahedron Lett. 2007, 48, 3171-3172
23. Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J. C.; Boireau, A.; Bour, Y.; Coleno, M. A.; Doble, A.; Doerflinger, G.; Huu, C. D.; Donat, M. H.; Duchesne, J. M.; Ganil, P.; Gueremy, C.; Honor, E.; Just, B.; Kerphirique, R.; Gontier, S.; Hubert, P.; Laduron, P. M.; Le Blevec, J.; Meunier, M.; Miquet, J. M.; Nemecek, C.; Mignani, S. Riluzole series. Synthesis and in vivo "antiglutamate" activity of 6-substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines J. Med. Chem. 1999, 42, 2828-2843
24. Ronning, D. R.; Klabunde, T.; Besra, G. S.; Vissa, V. D.; Belisle, J. T.; Sacchettini, J. C. Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines Nat. Struct. Biol. 2000, 7, 141-146
25. Stephan, J.; Mailaender, C.; Etienne, G.; Daffe, M.; Niederweis, M. Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatis Antimicrob. Agents Chemother. 2004, 48, 4163-4170