[Mechanism of action of macrolide antibiotic filipin on cell and lipid membranes].

The review deals with investigation of the mechanism of action of macrolide pentaene antibiotic filipin on cell and bilayer lipid membranes (BLM). The sterol hypothesis of the filipin mechanism of action is confirmed experimentally. The hemolytic and geneticocytological action of filipin, its action on virus infection and prion protein-associated diseases are discussed. The data on the mechanism of filipin action on BLM are presented. Filipin single ionic channels with conductance of 15-20 pS that is 3-4 times higher than that of the amphotericin channels were detected on cholesterol-containing membranes in filipin low concentration (1 x 10(-8) M) aqueous salt solution. Combined ionic channels of filipin and amphotericin B with conductance of 25-30 pS, that is 1.5-2 time lower than that of the clean filipin channels and 5 times higher that of the clean amphotericin B channels were also detected. The selectivity of filipin channels is mainly cationic. The potential of the penetrating ion on 10-fold gradient is +18 mV. The practical aspects of filipin application in biology, medicine and pharmacology are indicated.

[Red blood cells hemolysis under combined action of ultrasonic waves and polyene antibiotics].

Ultrasonic and induced hemolysis of red blood cells in the presence of alkyl derivatives of amphotericin B and levorin modified by the amino and carboxy groups was investigated. Amphotericin B derivatives such as metamphocin, ethamphocin and carboamphocin and levorin derivatives such as levoridon, isolevoridon and carbolevoridon were shown to have their own hemolytic activity in isotonic medium at concentrations of 10(-5) - 10(-4) M in erythrocyte suspension. The exposure of erythromycytes to pure dimethylsulfoxide (0.1-30%), the main solvent of polyene antibiotics, as well as to propamphocin and butamphocin did not induce hemolysis and had a stabilizing action an red blood cells during the ultrasonic hemolysis. It was suggested that changing of the mechanical strength of erythrocytes under the action of the polyenes was likely associated with impairment of microviscosity of the protein-lipid system of the erythrocyte membranes due to formation of structural ionic channels of molecular size.

[Mechanism of the interaction of the individual components of levorin and nystatin preparations with lipid membranes]. / Issledovanie mekhanizma vzaimodeistviia individual'nykh komponentov preparatov levorina i nistatina s lipidnymi membranami.

Mechanism of interaction between separate levorin and nystatin component and lipid membranes was studied. It was shown that components A0, A1, A2 and A3 of levorin and components A1, A2, A3 and B1 of nystatin had a markedly pronounced membranotropic activity. Ion channel assembly and membrane conductivity were irreversibly controlled by concentration and membrane potential. Changes in selectivity of biomolecular lipid membranes depended on the structure of the antibiotics. The action of the levorin and nystatin components was based on increasing membrane conductivity by the mechanism of ion channel formation with parameters altering in relation to the antibiotic structure. Recommendations for directed synthesis of the antibiotic derivatives with high therapeutic efficacy are presented.