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Biological studies revealed a higher antibacterial potency of quaternary <jats:italic>N<\/jats:italic>\u2010alkylammonium bromides of CLA as compared to AZM. SAR studies of CLA salts, including biological, conformation and molecular\u2010docking analysis, enriched by physicochemical parameters, showed the importance of less bulky and unsaturated substituent for an efficient docking mode at the ribosomal tunnel and good antibacterial potency against clinical and standard <jats:italic>Streptococcus pneumoniae<\/jats:italic> and <jats:italic>Streptococcus pyogenes<\/jats:italic> strains (MICs 0.25 or 0.5\u2005\u03bcg\/mL). These CLA salts also have an at least threefold lower cytotoxicity than reference antibiotics at comparable antibacterial activity against the <jats:italic>S. pneumoniae<\/jats:italic> clinical strain. Differences in antibacterial effects noted for AZM and CLA salts bearing less bulky <jats:italic>N<\/jats:italic>\u2010substituents can be better understood when their binding modes in the ribosomal tunnel are considered rather than their common low lipophilicity and excellent water solubility.<\/jats:p>","DOI":"10.1002\/cmdc.202000273","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T22:11:55Z","timestamp":1590617515000},"page":"1529-1551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis and Antibacterial Activity of New <i>N<\/i>\u2010Alkylammonium and Carbonate\u2010Triazole Derivatives within Desosamine of 14\u2010 and 15\u2010Membered Lactone Macrolides"],"prefix":"10.1002","volume":"15","author":[{"given":"Anna","family":"Janas","sequence":"first","affiliation":[{"name":"Faculty of Chemistry Adam Mickiewicz University  Uniwersytetu Pozna\u0144skiego 8 61-614 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