ety of drug delivery systems for anthracyclines have been reported. In most cases, the drugs were linked to high molecular compounds such as dextran, DNA and others.
Macrolides and polyenes. Macrolides are usually classified to include: proper macrolides having 12-, 14- or 16-membered macrocyclic lactone ring to which at least one sugar is bound, and polyenes having 26- to 38-atom lactone ring containing 2 to 7 unsaturated bonds. Besides the sugars bound to the lactone ring, an additional aromatic part is normally present in the polyene molecule. As to the biosynthesis, however, both macrolides and polyenes are synthesized in the same way using identical building units.represent a broad group of compounds and new substances have been incessantly added to the list, including hybrid compounds. A number of derivatives of the basic structure can be produced by one microorganism, on the other hand, however, the compounds can also be found in different microorganisms. Macrolides usually possess an antibacterial activity whereas polyenes are mostly fungicides.produced by Saccharopolyspora erythrea, together with oleandomycin and picromycin, belong to the best known 14-membered lactone ring macrolides. A novel erythromycin was prepared by the recombinant Saccharopolyspora erythrea strain [9]. Macrolides with a 16-membered ring are represented by tylosin, that is produced by Streptomyces fradiae, as well as by leucomycin, spiramycin, etc. synthesis of lactone ring is similar to that observed in the case of other polyketides. In contrast to aromatics, propionate and butyrate units are more often used in the biosynthesis, instead of acetate ones. The greatest difference, however, consists in the fact that, instead of aromatic rings, a lactone ring is formed. Keto- and methyl groups of the polyketide chain, from which macrolides are formed, are normally transformed more frequently.Nystatin is the best known polyene antibiotic. Candicidine is another well known antibiotic belonging to the polyene group. Its molecule includes p-aminoacetophenone as the terminal group. 4-amino benzoic acid (PABA) was identified as a precursor of the aromatic part of candicidine molecule.
The sugars found in macrolide and polyene molecules are not encountered in the structures of microbial cells. They include both basic and neutral sugar molecules. Often, L-forms are found. Sofar, at least 15 different sugars have been described to occur in macrolides and polyenes. All of them are 6-deoxy sugars; some of them are N-methylated, others have the methyl on either the oxygen or carbon atom. As it has been repeatedly proven, glucose is primarily incorporated into macrolide sugar residues. Also in Streptomyces griseus, glucose, mannose and galactose were incorporated to a greater extent into the mycosamine candicidine, as compared to its aglycon. The transformation of glucose to a corresponding sugar takes place in the form of the nucleoside diphosphate derivatives, which is similar to the situation found in the case of other antibiotics.
Avermectins .The molecule of avermectins [10] consists of a 16-membered, macrocyclic lactone to which the disaccharide oleandrose is bound (Fig. 15). Avermectins are produced by Streptomyces avermitillis. The macrocyclic ring of avermectins is synthesized, as other polyketides, by producing a chain from acetate, propionate and butyrate building units. Oleandrose (2,6-dideoxy - 3-O-methylated hexose) is synthesized from glucose.
Avermectins are potent antiparasitic compounds with a broad spectrum against nematode and anthropod parasites. They lack antifungal and antibacterial activities. They bind to a specific, high-affinity site present in nematodes but not in vertebrates. Its dosage for animal and human is extremely low. Ivermectin (22,23-dihydroavermectin B1) is a semisynthetic compound which is used to control internal and external parasites in animals. It is the most potent anthelmintic compound of all. Avermectins are also employed in human medicine and plant protection. Detailed reviews on the uses and biosynthesis of avermectins can be found in recent monographs.
Chloramphenicol .Chloramphenicol is produced by Streptomyces venezuelae [11]. However, at present the antibiotic is commercially produced using a fully synthetic process. In contrast to polyketides, the aromatic ring of chloramphenicol molecule is synthesized from glucose via chorismic acid and p-amino benzoic acid in the microbe.
Aminoglycosides. Streptomycin (Fig.4) is a well-known representative of aminoglycoside antibiotics. It is synthesized by many streptomycetes to produce a number of derivatives. The molecule of streptomycin consists of three components: streptidine, L-streptose and N-methyl-L-glucosamine. ...
