A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis

Science

Volumn 307, Issue 5707, 2005, Pages 223-227

  Andries, Koen ^a   Verhasselt, Peter ^a   Guillemont, Jerome ^b   Göhlmann, Hinrich W H ^a   Neefs, Jean Marc ^a   Winkler, Hans ^a   Van Gestel, Jef ^a   Timmerman, Philip ^a   Zhu, Min ^c   Lee, Ennis ^d   Williams, Peter ^d   De Chaffoy, Didier ^a   Huitric, Emma ^e   Hoffner, Sven ^e   Cambau, Emmanuelle ^f   Truffot Pernot, Chantal ^f   Lounis, Nacer ^f,g   Jarlier, Vincent ^f  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^b Campus de Maigremont   (France)

^c JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^d Johnson Johnson Pharmaceutical R D   (United Kingdom)

^e SWEDISH INSTITUTE FOR INFECTIOUS DISEASE CONTROL   (Sweden)

^f PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^g JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIA; DISEASES; PLASMAS; PROTONS;

MYOBACTERIAL GROWTH; TUBERCULOSIS;

DRUG THERAPY;

1 (6 BROMO 2 METHOXY 3 QUINOLINYL) 4 DIMETHYLAMINO 2 (1 NAPHTHYL) 1 PHENYL 2 BUTANOL; DIARYLQUINOLINE; ISONIAZID; PROTON PUMP; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; PYRAZINAMIDE; QUINOLINE DERIVATIVE; RIFAMPICIN; UNCLASSIFIED DRUG;

DRUG DEVELOPMENT; TUBERCULOSIS;

AMINO ACID SEQUENCE; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GROWTH; BLOOD LEVEL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG SENSITIVITY; HUMAN; MOUSE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; NORMAL HUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TUBERCULOSIS;

AMINO ACID SEQUENCE; ANIMALS; ANTITUBERCULAR AGENTS; BACTERIAL PROTON-TRANSLOCATING ATPASES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, BACTERIAL; DRUG THERAPY, COMBINATION; ENZYME INHIBITORS; HUMANS; MALE; MICE; MICROBIAL SENSITIVITY TESTS; MOLECULAR SEQUENCE DATA; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; POINT MUTATION; PROTEIN SUBUNITS; QUINOLINES; TUBERCULOSIS; TUBERCULOSIS, MULTIDRUG-RESISTANT;

BACTERIA (MICROORGANISMS); MYCOBACTERIUM; MYCOBACTERIUM TUBERCULOSIS; POSIBACTERIA;

EID: 19944429772     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1106753     Document Type: Article

References (22)

1. Global Alliance for TB Drug Development (www.tballiance.org).
2. E. L. Corbett et al., Arch. Intern. Med. 163, 1009 (2003).
3. UNAIDS, AIDS Epidemic Update 2004 (www.unaids.org/wad2004/report_pdf. html).
4. World Health Organization, Treatment of Tuberculosis (www.who.int/ docstore/gtb/publications/ttgnp/index.html).
5. R. J. O'Brien, P. P. Nunn, Am. J. Respir. Crit. Care Med. 163, 1055 (2001).
6. A. J. Claxton, J. Cramer, C. Pierce, Clin. Ther. 23, 1296 (2001).
7. J. Guillemont, Patent (International Publication Number: WO 2004/011436, International Publication Date: 5 February 2004).
8. See supporting data on Science Online.
9. R. Jain, B. Vaitilingam, A. Nayyar, P. B. Palde, Bioorg. Med. Chem. Lett. 13, 1051 (2003).
10. C. M. Kunin, W. Y. Ellis, Antimicrob. Agents Chemother. 44, 848 (2000).
11. M. R. Barbachyn, S. J. Brickner, Patent (International Publication Number: WO 93/09103, International Publication Date: 13 May 1993).
12. L. Savini, L. Chiasserini, A. Gaeta, C. Pellerano, Bioorg. Med. Chem. 10, 2193 (2002).
13. S. Vangapandu, M. Jain, R. Jain, S. Kaur, P. P. Singh, Bioorg. Med. Chem. 12, 2501 (2004).
14. K. Andries et al., data not shown.
15. S. H. Siddiqi, J. P. Libonati, G. Middlebrook, J. Clin. Microbiol. 13, 908 (1981).
16. M. Rao, T. L Streur, F. E. Aldwell, G. M. Cook, Microbiology 147, 1017 (2001).
17. G. Deckers-Hebestreit, K. Altendorf, Annu. Rev. Microbiol. 50, 791 (1996).
18. E. L. Nuermberger et al., Am. J. Respir. Crit. Care Med. 169, 421 (2004).
19. The BLOSUM62 matrix is used for scoring protein alignments. It is based on alignments with identity of at least 62% and contains scoring values for individual amino acid substitutions (27).
20. K. Godfrey, N. Engl. J. Med. 313, 1450 (1985).
21. S. Henikoff, J. G. Henikoff, Proc. Natl. Acad. Sci. U.S.A. 89, 10915 (1992).
22. We dedicate this paper to the memory of Dr. Paul Janssen, who inspired many of us. We thank K. Bush for testing several nonmycobacteria and S. Brown for testing H. pylori; B. Molenberghs, L. Vranckx, R. Willebrords, T. Gevers, P. Janssens, H. Szel, A. Van Dijck, F. Woestenborghs, L. Decrane, E. Pasquier, I. Csoka, A. Poncelet, D. Vernier, and A. Chauffour for technical assistance; B. Neys and P. Leemans for informatics expertise; and the Quintiles group at Guy's Drug Research Unit, London, who conducted the clinical studies. Portions of the genomic DNA sequencing, genome assembly, and mutation analysis were performed by 454 Life Sciences, Branford, CT 06405, USA. The genome sequence for M. smegmatis strain MC2 was licensed from The Institute for Genome Research, Rockville, MD 20850, USA. The RefSeq accession number for the genomic sequence (including the atpE gene) from M. tuberculosis is NC_000962. The protein sequence of the ATP synthase C chain, encoded by atpE gene, from M. tuberculosis is Swiss-Prot accession number P63691. The nucleotide sequence of the wild-type atpE gene from M. smegmatis has EMBL accession number AJ862722. See legend to Fig. 2 for more details. Patents pending: EP 04/02402.7 and EP 04/04720.0. Work at the Swedish Institute for Infectious Disease Control and Pitié- Salpêtrière School of Medicine was supported by grants from Johnson & Johnson Pharmaceutical Research and Development. V.J., C.T.-P., N.L., and E.C. are members of the Centre National de Référence de la Résistance des Mycobactéries aux Antituberculeux, and they gratefully acknowledge financial support from Association Française Raoul Follereau, INSERM (grant EMI 0004), and Ministère de l'Education Nationale et de la Recherche (grant UPRES EA 1S41).