Spermicidal, anti-HIV, and micellar properties of di- and trihydroxylated cationic surfactants

The syntheses of 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethyl-1-alkanaminium 1(p) and 2-hydroxy-N,N-bis(2-hydroxyethyl)-N-methyl-1-alkanaminium 2(p) bromides are described for the homologous series, tetradecanaminium (p=14) through octadecaminium (p=18). The critical micelle concentrations (cmc's), measured by conductivity at 25 and 37 degreesC, of the even-numbered members of the series show the expected linear dependence on chain length. All compounds display spermicidal and virucidal activity. Plots of minimum effective concentration (MEC) versus chain length in the Sander-Cramer spermicidal assay of I and 2 show a cut-off effect and a parabolic relationship, respectively. The best compounds-1(17) and 1(18)-have MECs (similar to0.12 mg mL (1)) slightly lower than that of the commercial spermicide nonoxynol-9 (N-9). Compounds 1(16) and 2(17) show the best anti-HIV activity in in-vitro, cell-free and cell-associated virus inactivation assays. Both are highly effective at 0.1 mg mL (1) in the cell-free assay and 0.5 mg mL (-1) in the cell-associated assay. Compound 1(16) shows the best combination of dual activity against sperm and HIV. In summary, hydroxylated cationic surfactants, 1 and 2, show promise as inexpensive topical, contraceptive microbicides. (C) 2002 Published by Elsevier Science Ltd.