Synthesis and characterization of pyridoxine,nicotine and nicotinamide salts of dithiophosphoric acids as antibacterial agents against resistant wound infection |
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Authors: | Trinh Dang Ilyas S Nizamov Ramazan Z Salikhov Leysan R Sabirzyanova Vyacheslav V Vorobev Tatyana I Burganova Marina M Shaidoullina Elvira S Batyeva Rafael A Cherkasov Timur I Abdullin |
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Institution: | 1. Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russia;2. Alexander Butlerov Institute of Chemistry, Kazan (Volga Region) Federal University, 420008 Kazan, 18 Kremlyovskaya St., Russia;3. A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov St., 420088 Kazan, Russia;4. Republican Clinical Hospital, 420064 Kazan, 138 Orenburg tract, Russia |
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Abstract: | The pyridine-derived biomolecules are of considerable interest in developing medicinal compounds with various specific activities. Novel ammonium salts of pyridoxine, (S)-(–)-nicotine and nicotinamide with O,O-diorganyl dithiophosphoric acids (DTPA) were synthesized and characterized. The complexation of chiral monoterpenyl DTPA, including (S)-(–)-menthyl, (R)-(+)-menthyl, (1R)-endo-(+)-fenchyl, (1S,2S,3S,5R)-(+)-isopinocampheolyl derivatives, with pyridoxine and nicotine provided effective antibacterial compounds 3a,b,e,f, and 5a,b,d,f with MIC values against Gram-positive bacteria as low as 10?µM (6?µg/mL). Two selected pyridoxine and nicotine salts based on menthyl DTPA 3a and 5a were similarly active against antibiotic-resistant bacteria from burn wounds including MRSA. The compounds had enhanced amphiphilic and hemolytic properties and effectively altered surface characteristics and matrix-secreting ability of P. aeroginosa and S. aureus. MBC/MIC ratios of 3a and 5a suggested the bactericidal mode of their action. Furthermore, the compounds exhibited moderate cytotoxicity towards human skin fibroblasts (IC50?=?48.6 and 57.6?µM, respectively, 72?h), encouraging their further investigation as potential antimicrobials against skin and wound infections. |
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Keywords: | Pyridoxine Nicotine Nicotinamide Dithiophosphoric acids Quaternary ammonium salts Monoterpenes Antibacterial agents Wound infection MRSA Cytotoxicity |
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