CINECA IRIS Institutional Research Information System
IRIS è la soluzione IT che facilita la raccolta e la gestione dei dati relativi alle attività e ai prodotti della ricerca. Fornisce a ricercatori, amministratori e valutatori gli strumenti per monitorare i risultati della ricerca, aumentarne la visibilità e allocare in modo efficace le risorse disponibili.
EnglishThe loss of human lives to tuberculosis (TB) continues essentially unabated as a result of poverty, synergy with the HIV/ AIDS pandemic, and the emergence of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis. Despite some recent successes, such as the discovery of the diarylquinoline drug TMC207 and the promise of the bicyclic nitroimidazole compounds , and because of the high attrition rate in drug development , much greater effort is required to find better drugs in order to meet the desired goals of killing persistent tubercle bacilli and reducing TB treatment duration from 6 to less than 3 months.New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZ), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in murine models of TB. Using genetics and biochemistry, the enzyme decaprenylphosphoryl- -D-ribose 2’-epimerase was identified as a major BTZ target. Inhibition of this enzymatic activity abolishes formation of decaprenylphosphoryl arabinose, a key precursor 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.
Scheda prodotto non validato
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo
| Titolo: | Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis | |
| Autori: | ||
| Data di pubblicazione: | 2009 | |
| Rivista: | ||
| Abstract: | The loss of human lives to tuberculosis (TB) continues essentially unabated as a result of poverty, synergy with the HIV/ AIDS pandemic, and the emergence of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis. Despite some recent successes, such as the discovery of the diarylquinoline drug TMC207 and the promise of the bicyclic nitroimidazole compounds , and because of the high attrition rate in drug development , much greater effort is required to find better drugs in order to meet the desired goals of killing persistent tubercle bacilli and reducing TB treatment duration from 6 to less than 3 months.New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZ), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in murine models of TB. Using genetics and biochemistry, the enzyme decaprenylphosphoryl- -D-ribose 2’-epimerase was identified as a major BTZ target. Inhibition of this enzymatic activity abolishes formation of decaprenylphosphoryl arabinose, a key precursor 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. | |
| Handle: | http://hdl.handle.net/11571/146011 | |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
File in questo prodotto:
Copyright © 2022