RESUMEN
Infections caused by antibiotic resistant bacteria are a major health concern throughout the world. It is well known that PFK-158 can enhance the antibacterial effect of polymyxin, but its own anti-bactericidal effect is rarely discussed. In order to investigate the anti-bactericidal effect of PFK-158 and its derivatives, PFK-158 and 35 derivatives were designed, synthesized, and evaluated for their antibacterial activities. Compounds A1, A3, A14, A15 and B6 exhibited potent antibacterial effect against both clinical drug sensitive and resistant Gram-positive bacteria, and they are 2-8 folds more potent than levofloxacin against Methicillin-resistant staphylococcus epidermidis (MRSE). A significant synergistic effect of these compounds and polymyxin against drug-resistant Gram-negative bacteria, which is similar to PFK-158 was also observed. The result can provided a new and broader prospect for the development of new medicine against drug-resistant bacteria.
Asunto(s)
Antibacterianos/farmacología , Enterococcus/efectos de los fármacos , Resistencia a la Meticilina/efectos de los fármacos , Piridinas/farmacología , Quinolinas/farmacología , Staphylococcus aureus/efectos de los fármacos , Resistencia a la Vancomicina/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Piridinas/síntesis química , Piridinas/química , Quinolinas/síntesis química , Quinolinas/química , Relación Estructura-ActividadRESUMEN
The inclusion complexes of beta-cyclodextrin (beta-CD) and HP-beta-cyclodextrin (HP-beta-CD) with caffeine, theophylline and theobromine were investigated by fluorimetry. Various factors affecting the formation of inclusion complexes were discussed in detail including forming time, pH effect and temperature. The results indicate that inclusion process was affected seriously by laying time and pH. The forming time of beta-CD inclusion complexes is much longer than that of HP-beta-CD. The optimum pH range is about 7-12 for caffeine, 8-10 for TP, 10.5-12 for TB. The intensities of their fluorescence increase with the decreasing of temperature. Their maximum excitation wavelengths are all in the range of 280-290 nm. The emission wavelength of caffeine and theophylline are both in the range of 340-360 nm, and that of theobromine is about 325 nm. The fluorescence signals are intensified with the increasing concentration of CD. The stoichiometry of the inclusion complexes of CD with these three methyl xanthine derivatives are all 1:1 and the formation constant are all calculated.