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Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis.

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Title: Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis.
Authors: Makarov, Vadim, Manina, Giulia, Mikusova, Katarina, Möllmann, Ute, Ryabova, Olga, Saint-Joanis, Brigitte, Dhar, Neeraj, Pasca, Maria Rosalia, Buroni, Silvia, Lucarelli, Anna Paola, Milano, Anna, De Rossi, Edda, Belanova, Martina, Bobovska, Adela, Dianiskova, Petronela, Kordulakova, Jana, Sala, Claudia, Fullam, Elizabeth, Schneider, Patricia, McKinney, John D.
Source: Science (pre-March 2025). 5/8/2009, Vol. 324 Issue 5928, p801-804. 4p.
Subjects: Benzothiazine, Mycobacterium tuberculosis, Pandemics, Antibacterial agents, Laboratory mice, Genetic research, Biochemical research, Therapeutics
Abstract: New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazln-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-β-D-ribose 2′-epimerase as a major BTZ target, inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
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  Data: Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis.
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  Data: <searchLink fieldCode="AR" term="%22Makarov%2C+Vadim%22">Makarov, Vadim</searchLink><br /><searchLink fieldCode="AR" term="%22Manina%2C+Giulia%22">Manina, Giulia</searchLink><br /><searchLink fieldCode="AR" term="%22Mikusova%2C+Katarina%22">Mikusova, Katarina</searchLink><br /><searchLink fieldCode="AR" term="%22Möllmann%2C+Ute%22">Möllmann, Ute</searchLink><br /><searchLink fieldCode="AR" term="%22Ryabova%2C+Olga%22">Ryabova, Olga</searchLink><br /><searchLink fieldCode="AR" term="%22Saint-Joanis%2C+Brigitte%22">Saint-Joanis, Brigitte</searchLink><br /><searchLink fieldCode="AR" term="%22Dhar%2C+Neeraj%22">Dhar, Neeraj</searchLink><br /><searchLink fieldCode="AR" term="%22Pasca%2C+Maria+Rosalia%22">Pasca, Maria Rosalia</searchLink><br /><searchLink fieldCode="AR" term="%22Buroni%2C+Silvia%22">Buroni, Silvia</searchLink><br /><searchLink fieldCode="AR" term="%22Lucarelli%2C+Anna+Paola%22">Lucarelli, Anna Paola</searchLink><br /><searchLink fieldCode="AR" term="%22Milano%2C+Anna%22">Milano, Anna</searchLink><br /><searchLink fieldCode="AR" term="%22De+Rossi%2C+Edda%22">De Rossi, Edda</searchLink><br /><searchLink fieldCode="AR" term="%22Belanova%2C+Martina%22">Belanova, Martina</searchLink><br /><searchLink fieldCode="AR" term="%22Bobovska%2C+Adela%22">Bobovska, Adela</searchLink><br /><searchLink fieldCode="AR" term="%22Dianiskova%2C+Petronela%22">Dianiskova, Petronela</searchLink><br /><searchLink fieldCode="AR" term="%22Kordulakova%2C+Jana%22">Kordulakova, Jana</searchLink><br /><searchLink fieldCode="AR" term="%22Sala%2C+Claudia%22">Sala, Claudia</searchLink><br /><searchLink fieldCode="AR" term="%22Fullam%2C+Elizabeth%22">Fullam, Elizabeth</searchLink><br /><searchLink fieldCode="AR" term="%22Schneider%2C+Patricia%22">Schneider, Patricia</searchLink><br /><searchLink fieldCode="AR" term="%22McKinney%2C+John+D%2E%22">McKinney, John D.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 5/8/2009, Vol. 324 Issue 5928, p801-804. 4p.
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  Data: <searchLink fieldCode="DE" term="%22Benzothiazine%22">Benzothiazine</searchLink><br /><searchLink fieldCode="DE" term="%22Mycobacterium+tuberculosis%22">Mycobacterium tuberculosis</searchLink><br /><searchLink fieldCode="DE" term="%22Pandemics%22">Pandemics</searchLink><br /><searchLink fieldCode="DE" term="%22Antibacterial+agents%22">Antibacterial agents</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+research%22">Genetic research</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemical+research%22">Biochemical research</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink>
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  Label: Abstract
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  Data: New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazln-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-β-D-ribose 2′-epimerase as a major BTZ target, inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=40088418
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        Value: 10.1126/science.1171583
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        Text: English
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      – SubjectFull: Benzothiazine
        Type: general
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      – SubjectFull: Pandemics
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