Antibacterial activity of N-benzenesulfonyl derivatives

MARTINEZ SR; MIANA GE; ALBESA I; MAZZIERI MR; BECERRA MC

Otro; III Reunión Internacional de Ciencias Farmacéuticas ? RICiFa 2014; 2014

UNC y UNR

The indiscriminate clinical use of many very efficient antibiotics has led to an unfortunate emergence of bacteria able to resist them. The call for greater effort to develop new classes of antibiotics is fully justified. As a part of an ongoing lead discovery project, a library of N-benzenesulfonyl derivatives of bioactive heterocyclic compounds was design and prepared. The approach was based on the combination of two groups that are known to be active, benzenesulfonyl (BS) and 1, 2, 3, 4-tetrahydroquinoline heterocycle (THQ). The objective of this study was to evaluate the antibacterial activity of BS-THQ and to investigate the possible mechanism of action of this compound. Minimum inhibitory concentration (MIC) of BS-THQ was determined by using the standard tube dilution method according to Clinical Laboratory Standard Institute (CLSI). The reactive oxygen species were evaluated by Nitro Tetrazolium Blue (NBT) assay, and by Fluorescent Microscopy. Electron microscopy transmission (TEM???) provides useful insight into the mechanism of action of antibacterial agent. The compound showed inhibitory activity against of Staphylococcus aureus ATCC 29213, S. aureus (MRSA) ATCC 43300 strains at 200 μg/mL. The generation of ROS in the sensitive strain was particularly higher than in the resistant one.The BS-THQ at sub-MIC induced 15.6% and 2.7% ¿de qué?, respectively, and the same results was obtained by the qualitative method (¿cuál?). When a suspension of S. aureus ATCC 29213 was incubated with BS-THQ at sub-MIC, to investigate how this compound affects the bacterial morphology, membrane lipid perturbation was appreciated by TEM. We proposed as a main mechanism of action the membrane disorganization and ROS generation, which compromises the viability of microorganisms.