title: Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine.
abstract: A series of 13 phosphonium salts on the basis of pyridoxine derivatives were synthesized and their antibacterial activity against clinically relevant strains was tested in vitro. All compounds were almost inactive against gram-negative bacteria and exhibited structure-dependent activity against gram-positive bacteria. A crucial role of ketal protection group in phosphonium salts for their antibacterial properties was demonstrated. Among synthesized compounds 5,6-bis[triphenylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (compound 20) was found to be the most effective towards Staphylococcus aureus and Staphylococcus epidermidis strains (MIC 5μg/ml). The mechanism of antibacterial activity of this compound probably involves cell penetration and interaction with genomic and plasmid DNA.
authors.affiliation: Research and Educational Center of Pharmacy, Kazan Federal University, Kazan 420008, Russian Federation.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pugachev
authors.forename: Nikita V
authors.initials: NV
authors.lastname: Shtyrlin
authors.forename: Lubov P
authors.initials: LP
authors.lastname: Sysoeva
authors.forename: Elena V
authors.initials: EV
authors.lastname: Nikitina
authors.forename: Timur I
authors.initials: TI
authors.lastname: Abdullin
authors.forename: Alfiya G
authors.initials: AG
authors.lastname: Iksanova
authors.forename: Alina A
authors.initials: AA
authors.lastname: Ilaeva
authors.forename: Rashid Z
authors.initials: RZ
authors.lastname: Musin
authors.forename: Eugeny A
authors.initials: EA
authors.lastname: Berdnikov
authors.forename: Yurii G
authors.initials: YG
authors.lastname: Shtyrlin
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011736:Pyridoxine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D009943:Organophosphorus Compounds; C113117:tributylmethyl phosphonium chloride; D011736:Pyridoxine