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We integrated bioinformatics and experimental methods to identify new chemical compounds able to inhibit the activity of ErmC. Based on the virtual screening of a ZINC database composed of 17 mln lead-like molecules, 29 compounds were chosen for experimental verification. 23 compounds decreased the minimal inhibitory concentration of erythromycin in Escherichia coli strain that overexpresses ErmC’. Among them inhibitor TC28 (ZINC code 32747906) with IC50 100 µM was non-toxic to HEK 293 cells. It served as a template for similarity-based virtual screening, which led to obtaining two derivatives TC3s (ZINC code 62022572) and TC4s (ZINC code 49032257) with IC50 116 µM and 110 µM, respectively. Analysis of models of TC3s and TC4s docked to the ErmC’structure revealed a competitive mode of inhibition while TC28 a non-competitive. The binding of TC28 is predicted to disrupt the substrate by the ErmC’. Our results provide a basis for the development of inhibitors against the Erm-family enzymes.