seco-Cyclothialidines: new concise synthesis, inhibitory activity toward bacterial and human DNA topoisomerases, and antibacterial properties.
J Med Chem
; 44(4): 619-26, 2001 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-11170652
ABSTRACT
seco-Cyclothialidines are a promising class of bacterial DNA gyrase B subunit inhibitors. A new seco-cyclothialidine derivative containing a dioxazine moiety, BAY 50-7952, was synthesized through a new concise pathway. One key step of the synthesis is the straightforward formation of the 2-aminothiazole derivative of S-tritylcysteine. In biological tests, BAY 50-7952 and other known seco-cyclothialidines exhibited high and selective activity toward bacterial DNA gyrase and toward Gram-positive bacteria. The dioxazine moiety and other similar groups were found to be important for the ability of the seco-cyclothialidines to penetrate bacterial membranes. The opposite enantiomer ((S)-form) of BAY 50-7952 was also synthesized, and neither significant target activity nor in vitro antibacterial activity were found, suggesting a highly selective fit of the (R)-form. Despite promising in vitro activity, only poor activity was found in the murine infection model.
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Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Inibidores Enzimáticos
/
Inibidores da Topoisomerase II
/
Bactérias Gram-Positivas
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Hidroxibenzoatos
/
Antibacterianos
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article