Scaffold-hopping from aminoglycosides to small synthetic inhibitors of bacterial protein biosynthesis using a pseudoreceptor model

Virtual screening was used to find replacements for aminoglycoside antibiotics that are able to block in vitrotranscription and translation. A pseudoreceptor model retrieved potent vanilloid derivatives as sugar-mimics. These bioactive antibiotic agents were retrieved by a two-step virtual screening process. ‘Fuzzy’ pharmacophore models allowed for finding alternative chemotypes with lower structural complexity and greater synthetic accessibility than the query.