New ionic liquids based on 5-fluorouracil: Tuning of BSA binding and cytotoxicity.

In this work, we describe the synthesis, interactions with bovine serum albumin, and cytotoxicity of new ionic liquids based on 5-fluorouracil (API-ILs) with different cations (imidazolium, choline, isoquinolinium, guanidinium). The secondary and tertiary structure of BSA in solutions with different concentrations of API-ILs was monitored by the circular dichroism (CD) technique. The addition of API-ILs does not lead to structural changes in BSA. A quenching of fluorescence spectra intensity of BSA in presence of all API-ILs was observed, allowing the quantification of binding between API-ILs and BSA. The preferred localization of both ions in API-ILs differs significantly depending on the structure of the cation according to molecular docking. The aggregation of BSA in presence of API-ILs was analyzed by the dynamic light scattering (DLS) method, revealing a moderate increase in particle size. Cytotoxicity and selectivity of API-ILs on cancer and normal cell lines were estimated, showing a clear modification of the pharmaceutic activity of ionic liquid compared to 5-fluorouracil.

Synthesis and characterization of pyridoxine, nicotine and nicotinamide salts of dithiophosphoric acids as antibacterial agents against resistant wound infection.

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.