Cationic Type I Amphiphiles As Modulators of Membrane Curvature Elastic Stress in Vivo

Recently we proposed that the antineoplastic properties observed in vivo for alkyl-lysophospholipid and alkylphosphocholine analogues are a direct consequence of the reduction of membrane stored elastic stress induced by these amphiphiles. Here we report similar behavior for a wide range of cationic surfactant analogues. Our systematic structure-activity studies show that the cytotoxic properties of cationic surfactants follow the same pattern of activity we observed previously for alkyl-lysophospholipid analogues, indicating a common mechanism of action that is consistent with the theory that these amphiphiles reduce membrane stored elastic stress. We note that several of the cationic surfactant compounds we have evaluated are also potent antibacterial and antifungal agents. The similarity of structure-activity relationships for cationic surfactants against microorganisms and those we have observed in eukaryotic cell lines leads us to suggest the possibility that the antibacterial and antifungal properties of cationic surfactants may also be due to modulation of membrane stored elastic stress.