Benzothiazinones Kill Mycobacterium tuberculosis by blocking Arabinan synthesis

Science

Volumn 324, Issue 5928, 2009, Pages 801-804

  Makarov, Vadim ^a,b   Manina, Giulia ^a,c   Mikusova, Katarina ^a,d   Möllmann, Ute ^a,e   Ryabova, Olga ^a,b   Saint Joanis, Brigitte ^a,f   Dhar, Neeraj ^g   Pasca, Maria Rosalia ^a,c   Buroni, Silvia ^a,c   Lucarelli, Anna Paola ^a,c   Milano, Anna ^a,c   De Rossi, Edda ^a,c   Belanova, Martina ^a,d   Bobovska, Adela ^a,d   Dianiskova, Petronela ^a,d   Kordulakova, Jana ^a,d   Sala, Claudia ^a,g   Fullam, Elizabeth ^a,g   Schneider, Patricia ^a,g   McKinney, John D ^g   Brodin, Priscille ^h   Christophe, Thierry ^h   Waddell, Simon ^a,i   Butcher, Philip ^a,i   Albrethsen, Jakob ^a,j   Rosenkrands, Ida ^a,j   Brosch, Roland ^a,f   Nandi, Vrinda ^a,k   Bharath, Sowmya ^a,k   Gaonkar, Sheshagiri ^a,k   Shandil, Radha K ^a,k   Balasubramanian, Venkataraman ^a,k   Balganesh, Tanjore ^a,k   Tyagi, Sandeep ^l   Grosset, Jacques ^l   Riccardi, Giovanna ^a,c   Cole, Stewart T ^a,g   more..

^a New Medicines for Tuberculosis (NM4TB) Consortium   (India)

^b BACH INSTITUTE OF BIOCHEMISTRY   (Russian Federation)

^c UNIVERSITY OF PAVIA   (Italy)

^d Physics and Informatics   (Slovakia)

^e HANS KNÖLL INSTITUTE   (Germany)

^f INSTITUT PASTEUR   (France)

^g EPFL   (Switzerland)

^h Institute Pasteur Korea   (South Korea)

ⁱ ST GEORGE S HOSPITAL   (United Kingdom)

^j STATENS SERUM INSTITUT   (Denmark)

^k ASTRAZENECA   (United Kingdom)

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

more..

Author keywords

[No Author keywords available]

Indexed keywords

1,3 BENZOTHIAZINON 4 ONE; 2 [2 METHYL 1,4 DIOXA 8 AZASPIRO[4.5]DEC 8 YL] 8 NITRO 6 (TRIFLUOROMETHYL) 4H 1,3 BENZOTHIAZIN 4 ONE; ARABINAN; ARABINOSE; BACTERIAL ENZYME; BTZ 038; BTZ 043; BTZ 044; DECAPRENYLPHOSPHORYL ARABINOSE; DECAPRENYLPHOSPHORYL BETA DEXTRO RIBOSE 2' EPIMERASE; ETHAMBUTOL; GREEN FLUORESCENT PROTEIN; ISONIAZID; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; 2 (2 METHYL 1,4 DIOXA 8 AZASPIRO(4.5)DEC 8 YL) 8 NITRO 6 (TRIFLUOROMETHYL) 4H 1,3 BENZOTHIAZIN 4 ONE; 2-(2-METHYL-1,4-DIOXA-8-AZASPIRO(4.5)DEC-8-YL)-8-NITRO-6-(TRIFLUOROMETHYL)-4H-1,3-BENZOTHIAZIN-4-ONE; ARABAN; DECAPRENYLPHOSPHORYL BETA D RIBOSE 2' EPIMERASE, MOUSE; DECAPRENYLPHOSPHORYL-BETA-D-RIBOSE 2'-EPIMERASE, MOUSE; ENZYME INHIBITOR; ISOMERASE; POLYSACCHARIDE; SPIRO COMPOUND; THIAZINE DERIVATIVE;

BACTERIUM; BIOCHEMISTRY; CELL ORGANELLE; DRUG; GENETIC ANALYSIS; LYSIS; TUBERCULOSIS;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERICIDAL ACTIVITY; CHRONIC DISEASE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; FLUORESCENCE MICROSCOPY; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MULTIDRUG RESISTANCE; MYCOBACTERIUM; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; TOXICITY TESTING; TREATMENT OUTCOME; TUBERCULOSIS; AMINO ACID SEQUENCE; ANIMAL; ANTIBIOTIC RESISTANCE; BACTERIAL GENE; BAGG ALBINO MOUSE; BIOSYNTHESIS; CELL WALL; CEREBROSPINAL FLUID; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MICROBIOLOGICAL EXAMINATION; MICROBIOLOGY; MOLECULAR GENETICS; SYNTHESIS;

BACTERIA (MICROORGANISMS); MYCOBACTERIUM TUBERCULOSIS;

AMINO ACID SEQUENCE; ANIMALS; ANTITUBERCULAR AGENTS; ARABINOSE; CELL WALL; DRUG RESISTANCE, BACTERIAL; ENZYME INHIBITORS; ETHAMBUTOL; GENE EXPRESSION REGULATION, BACTERIAL; GENES, BACTERIAL; MICE; MICE, INBRED BALB C; MICROBIAL SENSITIVITY TESTS; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MYCOBACTERIUM; MYCOBACTERIUM TUBERCULOSIS; POLYSACCHARIDES; RACEMASES AND EPIMERASES; SPIRO COMPOUNDS; THIAZINES; TUBERCULOSIS;

EID: 65649096556     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1171583     Document Type: Article

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27. We thank A. Deshpande, I. Heinemann, P. Højrup, K. Johnsson, M. K. N. Kumar, N. Kumar, L. Pagani, P. Marone, M. R. McNeil, I. Old, J. Reddy, S. Schmitt, P. Vachaspati, and C. Weigel for their help and support. Patents related to this work have been filed (WO/2007/134625, WO/2009/010163, and PCT/EP2008/001088). The NM4TB Consortium is funded by the European Commission (LHSP-CT-2005-018923), and microarray work at St George's Hospital, University of London, is supported by the Wellcome Trust (grant 062511). Microarray data are Minimum Information About a Microarray Experiment (MIAME)-compliant and deposited under accession number E-BUGS-80 at http://bugs.sgul.ac.uk/E-BUGS-80.