Novel Bis-Ammonium Salts of Pyridoxine: Synthesis and Antimicrobial Properties.

Autor: Shtyrlin NV; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Pugachev MV; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Sapozhnikov SV; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Garipov MR; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Vafina RM; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Grishaev DY; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Pavelyev RS; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Kazakova RR; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Agafonova MN; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Iksanova AG; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Lisovskaya SA; Kazan Scientific Research Institute of Epidemiology and Microbiology, Kazan 420015, Russia., Zeldi MI; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Krylova ES; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Nikitina EV; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Sabirova AE; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Kayumov AR; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia., Shtyrlin YG; Kazan (Volga region) Federal University, Scientific and Educational Center of Pharmaceutics, Kremlyovskaya St. 18, Kazan 420008, Russia.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2020 Sep 22; Vol. 25 (18). Date of Electronic Publication: 2020 Sep 22.
DOI: 10.3390/molecules25184341
Abstrakt: A series of 108 novel quaternary bis-ammonium pyridoxine derivatives carrying various substituents at the quaternary nitrogen's and acetal carbon was synthesized. Thirteen compounds exhibited antibacterial and antifungal activity (minimum inhibitory concentration (MIC) 0.25-16 µg/mL) comparable or superior than miramistin, benzalkonium chloride, and chlorhexidine. A strong correlation between the lipophilicity and antibacterial activity was found. The most active compounds had logP values in the range of 1-3, while compounds with logP > 6 and logP < 0 were almost inactive. All active compounds demonstrated cytotoxicity comparable with miramistin and chlorhexidine on HEK-293 cells and were three-fold less toxic when compared to benzalkonium chloride. The antibacterial activity of leading compound 5c 12 on biofilm-embedded Staphylococcus aureus , Staphylococcus epidermidis , Escherichia coli or Pseudomonas aeruginosa was comparable or even higher than that of the benzalkonium chloride. In vivo 5c 12 was considerably less toxic (LD 50 1705 mg/kg) than benzalkonium chloride, miramistine, and chlorhexidine at oral administration on CD-1 mice. An aqueous solution of 5c 12 (0.2%) was shown to be comparable to reference drugs efficiency on the rat's skin model. The molecular target of 5c 12 seems to be a cellular membrane as other quaternary ammonium salts. The obtained results make the described quaternary bis-ammonium pyridoxine derivatives promising and lead molecules in the development of the new antiseptics with a broad spectrum of antimicrobial activity.
Databáze: MEDLINE
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