Improved BM212 MmpL3 Inhibitor Analogue Shows Efficacy in Acute Murine Model of Tuberculosis Infection

PLoS ONE

Volumn 8, Issue 2, 2013, Pages

  Poce, Giovanna ^a   Bates, Robert H ^b   Alfonso, Salvatore ^a   Cocozza, Martina ^a   Porretta, Giulio Cesare ^a   Ballell, Lluís ^b   Rullas, Joaquin ^b   Ortega, Fátima ^b   De Logu, Alessandro ^c   Agus, Emanuela ^c   La Rosa, Valentina ^d   Pasca, Maria Rosalia ^d   De Rossi, Edda ^d   Wae, Baojie ^e   Franzblau, Scott G ^e   Manetti, Fabrizio ^f   Botta, Maurizio ^f   Biava, Mariangela ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b GLAXOSMITHKLINE   (Spain)

^c UNIVERSITY OF CAGLIARI   (Italy)

^d UNIVERSITY OF PAVIA   (Italy)

^e UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^f UNIVERSITY OF SIENA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1,5 PYRROLE DERIVATIVE; ISONIAZID; MOXIFLOXACIN; RIFAMPICIN; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG STRUCTURE; FEMALE; GENE TARGETING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIPOPHILICITY; LUNG TUBERCULOSIS; MAXIMUM PLASMA CONCENTRATION; MMPL3 GENE; MOUSE; MUTATOR GENE; NONHUMAN; PHYSICAL CHEMISTRY; POINT MUTATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTIBIOTICS, ANTITUBERCULAR; BACTERIAL PROTEINS; CELL LINE; FEMALE; HUMANS; MICE; MICROBIAL SENSITIVITY TESTS; MICROSOMES; MYCOBACTERIUM TUBERCULOSIS; PIPERAZINES; PYRROLES; TUBERCULOSIS;

EID: 84874297088     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0056980     Document Type: Article

References (20)

1. Global Tuberculosis Control: WHO report 2011, World Health Organization, Geneva (WHO/HTM/TB/2011.16).
2. Treatment of Tuberculosis: guidelines for national programmes 4th ed., World Health Organization, Geneva (WHO/HTM/TB/2009.420).
3. Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 global report on surveillance and response (2010) World Health Organization, Geneva (WHO/HTM/TB/2010.3).
4. Biava M, Fioravanti R, Porretta GC, Sleiter G, Ettorre A, et al. (1997) New toluidine derivatives with antimycobacterial and antifungal activities. Med Chem Res 7: 228-250.
5. Fioravanti R, Biava M, Donnarumma S, Porretta GC, Simonetti M, et al. (1996) Synthesis and microbiological evaluation of (N-heteroaryl)arylmethanamines and their Shiff bases. II Farmaco 51: 643-652.
6. Fioravanti R, Biava M, Porretta GC, Artico M, Lampis G, et al. (1997) N-substituted 1-aryl-2(1H-imidazol-1-yl)1-ethanamines with broad spectrum in vitro antimycobacterial and antifungal activities. Med Chem Res 7: 87-97.
7. Deidda D, Lampis G, Fioravanti R, Biava M, Porretta GC, et al. (1998) Bactericidal activities of the pyrrole derivative BM 212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother 42: 3035-3037.
8. Biava M, Porretta GC, Poce G, Battilocchio C, Alfonso S, et al. (2011) Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach. Chem Med Chem 6: 593-599.
9. Biava M, Porretta GC, Poce G, Supino S, Deidda D, et al. (2006) Novel diarylpirrole derivatives of BM212 endowed with high activity toward Mycobacterium tuberculosis and low cytotoxicity. J Med Chem 49: 4946-4952.
10. Biava M, Porretta GC, Poce G, Battilocchio C, Alfonso S, et al. (2010) Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin. Bioorg Med Chem 18: 8076-8084.
11. Cho SH, Warit S, Wan B, Hwang HH, Pauli GF, et al. (2007) Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother 51: 1380-1385.
12. Rullas J, García JI, Beltrán M, Cardona P-J, Cáceres N, et al. (2010) Fast standardized therapeutic-efficacy assay for drug discovery against tuberculosis. Antimicrob Agents Chemother 54: 2262-2264.
13. Coates A, Hu Y, Bax R, Page C, (2002) The future challenges facing the development of new antimicrobial drugs. Nat Rev Drug Discov 1: 895-910.
14. La Rosa V, Poce G, Ortiz Canseco J, Buroni S, Pasca MR, et al. (2012) MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob Agents Chemother 56: 324-331.
15. Domenech P, Reed MB, Barry CE 3rd (2005) Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. Infect Immun 73: 3492-3501.
16. Varela C, Rittmann D, Singh A, Krumbach K, Bhatt L, et al. (2012) MmpL genes are associated with mycolic acid metabolism in Mycobacteria and Corynebacteria. Chem Biol 19: 498-506.
17. Grzegorzewicz AE, Pham H, Gundi VA, Scherman MS, North EJ, et al. (2012) Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol 8: 334-341.
18. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, et al. (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 56: 1797-1809.
19. Stanley SA, Grant SS, Kawate T, Iwase N, Shimizu M, et al. (2012) Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening. ACS Chem Biol 7: 1377-1384.
20. Zhang M, Sala C, Hartkoorn RC, Dhar N, Mendoza-Losana A, et al. (2012) Streptomycin-starved Mycobacterium tuberculosis 18b, a drug discovery tool for latent tuberculosis. Antimicrob Agents Chemother 56: 5782-5789.