Novel berberine-based pharmaceutical salts with fatty acid anions: Synthesis, characterization, physicochemical properties

Abstract

Berberine (BBR), a quaternary isoquinoline alkaloid found in a Chinese herb medicine from Berberis species plants, was utilized to synthesize three new biocompatible berberine-based pharmaceutical salts, featuring three mid-chain fatty acid anions derived from animal and vegetable oils. Three salts [BBR][FA] were namely berberine caproate [BBR][CAP], berberine heptylate [BBR][HEP] and berberine octoate [BBR][OCT]. These compounds were characterized using 1H and 13C NMR, FTIR, ESI-MS, and thermogravimetric analyses. The solubility and octanol/water partition coefficient were evaluated in water and simulated body fluids (simulated gastric, simulated intestinal and simulated body fluids). The water solubility of [BBR][FA] was higher than that of salt precursor berberine chloride [BBR][Cl]. The minimum inhibitory concentration and minimum bactericidal or fungicidal concentration against three strains (Staphylococcus aureus, Bacillus subtilis and Candida albicans) were also examined. The results showed that they have similar antimicrobial activity to [BBR][Cl]. Furthermore, transport and volumetric properties (density and conductivity) were determined to investigate their aggregation and solvation behaviors in aqueous solution. The limiting molar conductivity, Ʌ0, critical micelle concentration, cmc, apparent molar volume at infinite dilution, V2,φ0, the apparent molar expansibility at infinite dilution, Eφ0, etc for [BBR][FA] were calculated. Effect of the length in alkyl chain of fatty acid anions in [BBR][FA] and temperature on the obtained properties as well as the nature of the interactions in aqueous [BBR][FA] solutions have been discussed.