Membrane permeabilization and perturbation induced by alkyl- biguanidium salts

Abstract

ABSTRACTAlkylbiguanidium salts show membrane perturbing properties toward simple phospholipid bilayer (liposomes) and complex phospholipid membranes (bacterial membranes). Compared to metformin and phenformin, alkylbiguanidium salts induce a more significant permeabilization of the phospholipid membranes, leading to highly selective H+/OH− ion transport and subsequent depolarization of the membrane. Although alkylbiguanidium salts with shorter C6 and C8 chains are too hydrophilic to be inserted into the membrane and perturb it, those with C10, C12, C14, and C16 alkyl chains show high membrane permeabilization and depolarization activity. In addition, the C10, C12, and C14 compounds possess interesting antimicrobial activity, and, at concentrations close to their minimal inhibitory concentrations, they show low hemolytic activity and toxicity.