RESUMO
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⯵M (6⯵g/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 (IC50â¯=â¯48.6 and 57.6⯵M, respectively, 72â¯h), encouraging their further investigation as potential antimicrobials against skin and wound infections.
Assuntos
Antibacterianos/farmacologia , Niacinamida/farmacologia , Nicotina/farmacologia , Fosfatos/farmacologia , Piridoxina/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Fibroblastos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Niacinamida/síntese química , Niacinamida/química , Niacinamida/toxicidade , Nicotina/síntese química , Nicotina/química , Nicotina/toxicidade , Fosfatos/síntese química , Fosfatos/química , Fosfatos/toxicidade , Piridoxina/síntese química , Piridoxina/química , Piridoxina/toxicidade , Staphylococcus epidermidis/efeitos dos fármacosRESUMO
A new reaction of elemental phosphorus (P4) with elemental sulfur and 1,3-propylene glycol in the presence of different amines has been investigated. Ammonium salts of O,O'- alkylenedithiophosphoric acids have been observed as main products of the reaction. Octathiotetraphosphetane ammonium salts were formed as minor products. The reaction is characterized by a complete conversion of white phosphorus and is not accompanied by the release of hydrogen sulfide. The crystal structure features's of diethylammonium salt of O,O'-propylenedithiophosphoric acid were determined using single crystal X-ray diffraction. Piperidinium salt of octathiotetraphosphetane in DMSO and DMF solutions possess significant antifungal activity against Candida albicans.