Antifungal Macrocycle Antibiotic Amphotericin B—Its Present and Future. Multidisciplinary Perspective for the Use in the Medical Practice

Abstract—

This review is devoted to a broad analysis of the results of studies of the effect of macrocyclic antifungal polyene antibiotic amphotericin B on cell membranes. A detailed study of polyenes has shown that some of them can have not only antifungal, but also antiviral and antitumor effects. Under conditions of global pandemic fungal pathology develops especially quickly and in this case leads to invasive aspergillosis, which contributes to the complication of coronavirus infection in the lungs and even secondary infection with invasive aspergillosis. The treatment of an invasive form of bronchopulmonary aspergillosis is directly related to the immunomodulatory and immunostimulating properties of the macrocyclic polyene drug amphotericin B. The article presents experimental data on the study of the biological activity and membrane properties of amphotericin B and the effect of its chemically modified derivatives, as well as liposomal forms of amphotericin B on viral, bacterial and fungal infections. The mechanism of action of amphotericin B and its analogues is based on their interaction with cellular and lipid membranes, followed by formation of ion channels of molecular size in the membranes. The importance of these studies is that polyenes are sensitive to membranes that contain sterols of a certain structure. The analysis showed that pathogenic fungal cells containing ergosterol were 10−100 times more sensitive to polyene antibiotics than host cell membranes containing cholesterol. The high sterol selectivity of the action of polyenes opens broad prospects for the use of polyene antifungal drugs in practical medicine and pharmacology in the treatment of invasive mycoses and the prevention of atherosclerosis. In this context, it should be noted that polyene antibiotics are the main tool in the study of the biochemical mechanism of changes in the permeability of cell membranes for energy-dependent substrates. Chemical and genetic engineering transformation of the structure of polyene antibiotic molecules opens prospects for the identification and creation of new biologically active forms of the antibiotic that have a high selectivity of action in the treatment of pathogenic infections.