title: Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives.
abstract: A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistantS. aureusstrains with MICs in the range of 0.5-2μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negativeE. coliandP. aeruginosastrains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest inS. typhimuriumshowed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies.
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia.
authors: Nikita V
authors: NV
authors: Shtyrlin
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia.
authors: Sergey V
authors: SV
authors: Sapozhnikov
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia.
authors: Albina S
authors: AS
authors: Galiullina
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia.
authors: Airat R
authors: AR
authors: Kayumov
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia.
authors: Oksana V
authors: OV
authors: Bondar
authors: Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, B. Pirogovskaya St. 11, Moscow 119021, Russia.
authors: Elena P
authors: EP
authors: Mirchink
authors: Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, B. Pirogovskaya St. 11, Moscow 119021, Russia.
authors: Elena B
authors: EB
authors: Isakova
authors: Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, B. Pirogovskaya St. 11, Moscow 119021, Russia.
authors: Alexander A
authors: AA
authors: Firsov
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia; Institute of Physiologically Active Compounds of Russian Academy of Sciences, Severnyi Pr. 1, Chernogolovka, Moscow 142432, Russia.
authors: Konstantin V
authors: KV
authors: Balakin
authors: Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, Kazan 420008, Russia.
authors: Yurii G
authors: 0000-0002-2777-719X
authors: YG
authors: Shtyrlin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D011736:Pyridoxine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D000644:Quaternary Ammonium Compounds; C004675:4-deoxypyridoxine; D011736:Pyridoxine