RESUMEN
A series of novel 5-O-(4',6'-O-dimodified)-mycaminose 14-membered ketolides were assessed for their in vitro antibacterial activities against a panel of sensitive and resistant pathogens. Compound 1 and compound 2, two ester analogs, showed the best antibacterial activities against several macrolide-sensitive and macrolide-resistant strains. These results indicated that introducing ester to 6-OH and a small volume ether substituent to the 4-OH of mycaminose could improve the antibacterial activities of ketolides.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Cetólidos/química , Cetólidos/farmacología , Bacterias/efectos de los fármacos , Estructura MolecularRESUMEN
A new class of 1-[(1R,2S)-2-fluorocyclopropyl]ciprofloxacin (CPFX)-1,2,4-triazole-5(4H)-thione hybrids 6a - 6o was designed, synthesized and evaluated for their in vitro antibacterial activities against a panel of clinically important drug-sensitive and drug-resistant Gram-positive and Gram-negative pathogens. Our results revealed that all hybrids 6a - 6o had great potency against the tested strains, especially Gram-negative pathogens. The synthesized hybrids were more potent than the parent 1-[(1R,2S)-2-fluorocyclopropyl]CPFX (1) and comparable to CPFX and levofloxacin against the majority of the tested pathogens, worth to be further investigated.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Ciprofloxacina/análogos & derivados , Ciprofloxacina/farmacología , Diseño de Fármacos , Triazoles/química , Triazoles/farmacología , Antibacterianos/síntesis química , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Ciprofloxacina/síntesis química , Halogenación , Humanos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Tionas/síntesis química , Tionas/química , Tionas/farmacología , Triazoles/síntesis químicaRESUMEN
Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.