Chemical validation of DegS as a target for the development of antibiotics with a novel mode of action.

Chemical validation of DegS as a target for the development of antibiotics with a novel mode of action. ChemMedChem. 2019 Apr 04;: Authors: Bongard J, Schmitz AL, Wolf A, Zischinsky G, Pieren M, Schellhorn B, Bravo-Rodriguez K, Schillinger J, Koch U, Nussbaumer P, Klebl B, Steinmann J, Buer J, Sanchez-Garcia E, Ehrmann M, Kaiser M Abstract Despite the availability of hundreds of antibiotic drugs, infectious diseases continue to remain one of the most notorious health issues. In addition, the disparity between the spreading of multidrug resistant pathogens and the development of novel classes of antibiotics exemplify an important unmet medical need that can only be addressed by identifying novel targets. Here we demonstrate by the development of the first in vivo active DegS inhibitors based on a pyrazolo[1,5-a]-1,3,5-triazine scaffold that DegS and the cell envelope stress response pathway sigmaE represent a target for generating antibiotics with a novel mode-of-action. Moreover, DegS inhibition is synergistic to well-established membrane perturbating antibiotics thereby opening promising avenues for rational antibiotic drug design. PMID: 30945468 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research