Rabanal Anglada, FrancescGrau Campistany, AriadnaVila Farrés, XavierGonzález-Linares, J. (Javier)Borràs Suárez, MiquelVila Estapé, JordiManresa Presas, Ma. Ángeles (María Ángeles)Cajal Visa, Yolanda2015-07-072015-07-072015-05-292045-2322https://hdl.handle.net/2445/66210Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.11 p.application/pdfengcc-by-nc-nd (c) Rabanal Anglada, Francesc et al., 2015http://creativecommons.org/licenses/by-nc-nd/3.0/esDesenvolupament de medicamentsMembranes (Biologia)PèptidsToxicitat dels medicamentsAntibiòticsBacteris patògensDrug developmentMembranes (Biology)PeptidesDrug toxicityAntibioticsPathogenic bacteriainfo:eu-repo/semantics/article6519052015-07-07info:eu-repo/semantics/openAccess26024044