Main trends in the design of semi-synthetic antibiotics of a new generation

Abstract

This review summarizes main advances achieved by Russian researchers in the synthesis and characterization of semi-synthetic antibiotics of a new generation in the period from 2004 to 2019. The following classes of compounds are considered as the basis for modification: polycyclic antibacterial glycopeptides of the vancomycin group, classical macrolides, antifungal polyene macrolides, the antitumour antibiotic olivomycin A, antitumour anthracyclines and broad-spectrum antibiotics, in particular, oligomycin A, heliomycin and some other. Main trends in the design of modern anti-infective and antitumour agents over this period are considered in relation to original natural antibiotics, which have been independently discovered by Russian researchers. It is shown that a new type of hybrid structures can, in principle, be synthesized based on glycopeptides, macrolides and other antibiotics, including heterodimers containing a new benzoxaborole pharmacophore. The review addresses the influence of the length of the spacer between two antibiotic molecules on the biological activity of hybrid structures. A combination of genetic engineering techniques and methods of organic synthesis is shown to be useful for the design of new potent antifungal antibiotics based on polyenes of the amphotericin B group. Many new semi-synthetic analogues exhibit important biological properties, such as a broad spectrum of activity and low toxicity. Emphasis is given to certain aspects related to investigation of a broad range of biological activity and mechanisms of action of new derivatives. The bibliography includes 101 references.