RESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have caused an increasing mortality rate, which means that antibiotic resistance is becoming an important health issue. In the course to screen new agents for resistant bacteria, we identified that a series of isatin-ß-thiosemicarbazones (IBTs) could inhibit the growth of MRSA and VRE. This was the first time that the "familiar" IBT compounds exhibited significant anti Gram-positive pathogen activity. Against a clinical isolated MRSA strain, 20 of the 51 synthesized compounds showed minimum inhibitory concentration (MIC) data of 0.78 mg/L and another 12 novel compounds had MICs of 0.39 mg/L. Moreover, these compounds also inhibited Enterococcus faecalis and VRE at similar levels, indicating that IBTs might have different mode of action compared with vancomycin. For these IBTs, comparative field analysis (CoMFA) models were further established to understand the structure-activity relationships in order to design new compounds from steric and electrostatic contributions. This work has suggested that IBTs can be considered as potential lead compounds to discover antibacterial inhibitors to combat drug resistance.
Asunto(s)
Antibacterianos/farmacología , Isatina/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Tiosemicarbazonas/farmacología , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Isatina/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Tiosemicarbazonas/químicaRESUMEN
46 Novel nonsymmetrical aromatic disulfides containing [1,3,4]thiadiazole or [1,3,4]oxadiazole groups were synthesized and their biological activities were evaluated as inhibitors of acetohydroxyacid synthase (AHAS, EC 2.2.1.6). Besides their strong in vitro inhibition against plant AHAS, compounds 3e and 3f also display 80-100% post-emergence herbicidal activities in greenhouse bioassay at 1500g /ha dosage. The assay of exogenous branched-chain amino acids supplementation on rape root growth of 3e suggests that the herbicidal activity has relationship with AHAS inhibition.
Asunto(s)
Acetolactato Sintasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Hidrocarburos Aromáticos/farmacología , Sulfuros/farmacología , Acetolactato Sintasa/metabolismo , Arabidopsis/enzimología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Hidrocarburos Aromáticos/síntesis química , Hidrocarburos Aromáticos/química , Estructura Molecular , Oxadiazoles/química , Relación Estructura-Actividad , Sulfuros/síntesis química , Sulfuros/química , Tiadiazoles/químicaRESUMEN
A total of 29 novel sulfenamide compounds were synthesized, spectroscopically characterized and evaluated in vitro for antimicrobial activity against various infectious pathogens. Compounds 1b and 2c exhibited potent inhibition against clinical Methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) values of 1.56 µg/mL.
