A structure-activity study of spermicidal and anti-HIV properties of hydroxylated cationic surfactants.

The syntheses of 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethylhexadecan-1-aminium chloride [1(16)Cl] and iodide [1(16)I], 2-hydroxy-N,N,N-trimethylhexadecan-1-aminium chloride (6), N-(2-hydroxyethyl)-N,N-dimethylhexadecan-1-aminium chloride (8), N,N-bis(2-hydroxyethyl)-N-methylhexadecan-1-aminium chloride (11), and 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethyl-4-oxahexadecan-1-aminium chloride (14) are reported along with the critical micelle concentrations (cmcs), as measured by conductivity at 25 degrees C, of 1(16)Cl, 1(16)I, 6, 8, 11, and N,N,N-trimethylhexadecan-1-aminium chloride (12). All compounds display spermicidal and virucidal activity. A plot of minimum effective concentration (MEC) in the Sander-Cramer spermicidal assay and cmc shows that 1(16)Cl and 6 have the best spermicidal activity and highest cmcs. Compounds 8, 11, and 1(16)Cl are the most active at 0.05 mg mL(-1) against cell-free and cell-associated virus. In conclusion, 1(16)Cl shows the best combination of dual activity against sperm and HIV; it is a promising candidate for further preclinical studies as a topical, contraceptive microbicide.