After decades, the
glycopeptide vancomycin is still the preferred
antibiotic against resistant strains of Gram-positive bacteria. Although its clinical use is strictly regulated, the gradual spread of
vancomycin-resistant bacteria, such as
glycopeptide-resistant and glycopeptide-intermediate Staphylococcus aureus and
vancomycin-resistant Enterococcus spp., is a serious health problem. Based on the literature data and previous studies, our main goal was to assess the antimicrobial potential and to study the structure-activity relationship of new
eremomycin aminoalkylamides. We designed and synthesized a series of new
eremomycin amides in which
eremomycin is conjugated with a hydrophobic arylalkyl group via an alkylenediamine spacer, and tested their antibacterial activities on a panel of Gram-positive strains that were sensitive and resistant to a "gold-standard"
vancomycin. Based on the data obtained, the structure-activity relationships were investigated, and a lead compound was selected for in-depth testing. Research carried out using an in vivo model of staphylococcus
sepsis, acute toxicity studies, and the estimated therapeutic index also showed the advantage of the selected
eremomycin amide derivative in particular, as well as the chosen direction in general.