Sulfonamides ELISA Kit

Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 mu g/mL (acetazolamide) to MIC = 0.007 mu g/mL (22) and 1 mu g/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative alpha-carbonic and gamma-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.

As the orexin signaling system is crucial for the regulation of the sleep/wake cycle, inhibitors of orexin-1 and orexin-2 receptors are of significant interest in the treatment of insomnia. Herein, a series of novel azacycloheptane sulfonamide derivatives were designed and synthesized, and all the compounds were evaluated as potential orexin receptor inhibitors by FLIPR Tetra calcium assay. A majority of the tested azacycloheptane sulfonamide derivatives showed OX1R and OX2R inhibitory activity. Chloro-substituted derivatives functionalized at the C5 or C6 position of the benzoxazole group exhibited better inhibitory activity for OX1R and OX2R than unsubstituted derivatives functionalized at C5 or C6. In addition, phenyl group modification had positive effects on the inhibitory activities, and an electron-withdrawing fluorine group at theorthoormetaposition of the phenyl ring improved the OX2R inhibitory activity of the derivatives. This suggests that azacycloheptane sulfonamide derivatives are promising scaffolds for the development of OX1R and OX2R antagonists.