Macrolides classification

Antibiotics can be classified according to their effects on the biochemistry or molecular biology of pathogens. There are ribosomal inhibitors (macrolides), cell wall disrupters 0-lactams), DNA disturbers (fluoroquinolones), and metabolic poisons (trimethoprim-sulfamethoxazole). Antibiotics also can be classified according to whether they are static (inhibitory) or cidal (lethal). The classification of drugs as either static or cidal is based on laboratory assessment of the interaction of pathogen and antibiotic drug. 

Figure 1.6 Number of antibiotic prescriptions per 1000 inhabitants per antibiotic anatomical therapeutic chemical (ATC) classification in 13 European countries in 1997. In parentheses are the ATCs used by the WHO. Tet = tetracyclines, Pen = penicillin, Ex-Pen = extended-spectrum penicillins, B-Lac = (3-lactamase-sensitive penicillins. Cep = cephalosporins, TMP = trimethoprim (alone or in combination), Mac + Lin = macrolides and lincosamides, Mac = macrolides, Lin = lincosamides. Ami = aminoglycosides, and Qui = quinolone. The 13 countries are SP = Spain, GR = Greece, BG = Belgium, PR = Prance, PL = Portugal, IT = Italy, PI = Pinland, UK = United Kingdom, DE = Denmark, AU = Austria, GE = Germany, SW = Switzerland, and NL = Netherlands. (Based on data from Molstad et al., 2002.)...

Macrolide antibiotics are a homogeneous group of antimicrobial drugs that have been used to treat clinical infections for several decades. The most clinically useful classification of the macrolides is based on the size of the lactone ring that forms the chemical nucleus of each macrolide molecule [1, 2]. The 14- and 15-membered macrolides include erythromycin, clarithromycin, dirithromycin, roxithromycin, and azithromycin. Erythromycin is the oldest and still the most important of the macrolide antibiotics because it is a useful alternative to penicillin G. It is one of the safest antibiotics available. Clarithromycin and azithromycin have shown some advantages over erythromycin in their antibacterial activity,... 

A. Classification and Pharmacokinetics The lincosamides lincomycin and clindamycin inhibit bacterial protein synthesis via a mechanism similar to that of the macrolides, though they are not chemically related. Mechanisms of resistance include methylation of the binding site on the 50S ribosomal subunit and enzymatic inactivation. Cross-resistance between lincosamides and macrolides is common. Good tissue penetration occurs after oral absorption. The lincosamides are eliminated partly by metabolism and partly by biliary and renal excretion. 

A second aid to the chemical classification of polyenes is the presence in the antibiotic of either a hexosamine sugar or an aromatic moiety. The presence of sugars is a characteristic of macrolide antibiotics. Polyene hexosamines are similar to the sugars present in the non-polyene macrolides [27]. The structure of polyene hexosamines has been determined and with one exception, the carbohydrate is mycosamine [28—30], the structure of which has been unequivocally established by chemical synthesis [31] as 3-amino-3,6-dideoxy-D-mannopyranose (1). The sugar perosamine, 4-amino4,6-dideoxy-D-mannose (2), an isomer of mycosamine, has been isolated from perimycin [31,32]. 

Following the biogenetic classification, we first address macrolactones, divided into the main family groups that have received synthetic attention via RCM (re-sorcinylic, salycilates, other antibiotic macrolides, macrocyclic musks, epothilones, amphidinolides, other polyketides, and natural cyclophanes), then the terpenoids, followed by the macrocycles obtained from the amino acid metabolism (lactams, depsipeptides, alkaloids), and finally the glycolipids. 

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