New quaternary ammonium pyridoxine derivatives: synthesis and antibacterial activity
| Autor: | Еlena S. Krylova, Denis Yu. Grishaev, Konstantin V. Balakin, Alfiya G. Iksanova, Yurii G. Shtyrlin, Nikita V. Shtyrlin, Еlena V. Nikitina, Alina E. Zamaldinova, Airat R. Kayumov, Sergey V. Sapozhnikov |
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| Rok vydání: | 2017 |
| Předmět: |
010405 organic chemistry
Chemistry Organic Chemistry 010402 general chemistry medicine.disease_cause Pyridoxine 01 natural sciences In vitro 0104 chemical sciences Benzalkonium chloride Biochemistry Lipophilicity medicine General Pharmacology Toxicology and Pharmaceutics Antibacterial activity Cytotoxicity Staphylococcus Genotoxicity medicine.drug |
| Zdroj: | Medicinal Chemistry Research. 26:3188-3202 |
| ISSN: | 1554-8120 1054-2523 |
| Popis: | A diverse library of 34 new quaternary mono-ammonium and bis-ammonium pyridoxine derivatives was synthesized, and their antibacterial activity against several clinically relevant bacterial strains was evaluated in vitro. Several mono-ammonium compounds demonstrated high antibacterial activity against methicillin-resistant Staphylococcus strains with minimum inhibitory concentrations in the range of 0.5–8 µg/mL, which exceeded activity of miramistin and was comparable to that of benzalkonium chloride. SOS-chromotest in Salmonella typhimurium showed the lack of DNA-damage activity for all active compounds. A clear correlation has been observed between the lipophilicity of the obtained compounds and their activity against the studied Gram-positive bacterial strains. Cytotoxicity studies on HEK-293 cells demonstrated that some of the active compounds were less toxic than the reference drugs. Antibacterial activity studies in the presence of CaCl2 suggested that the cell wall damage associated with the removal of Ca2+ ions from the bacterial membrane is one of the possible mechanisms of antibacterial activity. The obtained results make the described active compounds a promising starting point for the development of new antibacterial therapies. |
| Databáze: | OpenAIRE |
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