Macrolides

Macrolides 

an extensive group of antibiotics that contain a polymerous lactone cycle.

All known macrolides are isolated from soil fungi of the genus Streptomyces. They are divided into two subgroups, according to their structure and physiological effect. The first subgroup (more than 30 antibiotics) includes lactones whose carbon skeleton consists of a fatty polyoxyacid that is saturated or that contains one or two double bonds with one or two hydroxyl groups bonded to the carbohydrate residues. The compounds of the subgroup (for example, pikromycin, methymycin, narbomycin, oleandomycin, erythromycin, lancamycin, magnamycin, carbomycin B, macrocin, and leukomycin A) are colorless crystals that are readily soluble in polar organic solvents, have weakly basic properties, and are active against most gram-positive and some gram-negative bacteria (brucellae), rickettsiae, and, sometimes, cocci. Their mode of action consists in the suppression of protein synthesis in the cells of the microorganisms.

The second subgroup (about 30 antibiotics) consists of lactones whose carbon skeleton contains, in addition to hydroxyl groups, from four to seven conjugated double bonds. In most of the macrolides of this type (also called polyene antibiotics), one or two hydroxyl groups are bonded to amino sugar residues. The compounds of this group (Filipin, nystatin, amphotericin B, pimaricin, lagosin, and fungichromin, for example) are yellow crystals that decompose in light. They are active against fungi and yeasts but are only weakly bacteriostatic. Their mode of action consists in disruption of the functions of the cytoplasmic membranes, owing to the formation of molecular complexes with sterols in the membranes. The biosynthesis of macrolides by their producer-fungi follows the pattern of the biosynthesis of fatty acids.

REFERENCES

Khimiia antibiotikov, 3rd ed., vol. 1. Moscow, 1961.
Sazykin, Iu. O. Antibiotiki kak ingibitory biokhimicheskikh protsessov. Moscow, 1968.
Mekhanizm deistviia antibiotikov. Moscow, 1969. (Collection of articles; translated from English.)
Biogenesis of Antibiotic Substances. Prague, 1965.

E. P. SEREBRIAKOV