Macrolide chemical structures

Fig. 1 Chemical structures of some of the most important antibiotics used nowadays divided into the most representative families fluoroquinolones, sulfonamides, penicillins, macrolides, and tetracyclines. Another important antibiotic, chloramphenicol, is also shown...

Fig. 3.4 Chemical structures of commonly used macrolides and lincosamides.

Research to date focused on isolating insecticidal prototype leads from marine origin has resulted in the report of about 40 active compounds.44 In an attempt to summarize these compounds and their activity margins, they have been categorized into seven classes of chemical structures polyhalogenated monoterpenes, polyhalogenated C15-metabolites, diterpenes, peptides and amino acids, phosphate esters, sulfur-containing derivatives, and macrolides. 

Figure 1 Structural and bioconverting relationships among tylosin, AIV, and its related acyltylosins. (A) Chemical structures of tylosin, AIV, and its related acyltylosins. (B) Biotransformation of tylosin to AIV by two types of macrolide acyltransferases in S. ther-motolerans 3-O-acyltransferase and 4"-0-acyltransferase catalyze acetylation at the 3-hydroxyl group of tylonolide and isovalerylation at the 4"-hydroxyl group of mycarose, respectively.

Fig. 4.6 Chemical structures of MLSb antibiotics. Macrolides are comprised of a central lactone ring of 14, 15 or 16 atoms, from which extend various sugar groups and functional groups. Lincosamides are comprised of two...

While broad spectrum anthelmintics (macrolide endectocides, benzimidazole carbamates, tetrahydropyrimidines) largely overlap in the range of endoparasites (mainly nematodes) they affect, the various anthelmintic classes (based on chemical structure) differ in mechanism of action, degree of activity and in pharmacokinetic properties (bioavailability, tissue distribution and... 

Further antibiotics, mainly derived from actinomycetes, are used for special applications in human and veterinary medicine [20]. These compounds have numerous chemical structures. The macrolides, tetracyclines, aminoglycosides, glycopeptides, and ansamycins for instance are used in antibacterial treatment whereas the anthracyclines reached the market to supplement anticancer chemotherapy. The fairly toxic polyether-type antibiotics are preferably used as anticoccidial agents. Due to the dramatically increasing resistance of clinical important bacterial strains new targets for the discovery of novel types of antibacterial agents are urgently needed. 

Werner, G., Hagenmaier, H., Drautz, H., Baumgartner, A., and Zaehner, H. (1984). Metabolic products of microorganisms. 224. Bafilomycins, a new group of macrolide antibiotics. Production, isolation, chemical structure and biological activity. J. Antibiot. 37, 110-117. 

Rapamycin (sirolimus) is another macrolide antibiotic that possesses potent immunosuppressant activity. Rapamycin has a chemical structure partially similar to that of tacrolimus (Fig. 2). It was first isolated from Streptomyces hygro-scopicus strains found in soil obtained on Rapa Nui (Easter Island), hence the name rapamycin [19, 20]. This compound was initially investigated as an antifungal agent and later found to have immunosuppressive activity [21]. Rapamycin also binds to FKBP, but its immunosuppressive mechanisms are distinct from those of tacrolimus and cyclosporin in that it does not act via the calcineurin pathway [22, 23]. The immunosuppressive effects of rapamycin result from its inhibition of T-cell [23, 24] and B-cell [25] proliferation. The key effect on those cells results from the blocking of the signals of several cytokines (IL-2 and IL-4), leading to interruption of the cell cycle from the G, to the S phase. Unlike tacrolimus, the complex of rapamycin and FKBP-12 does not inhibit the dephosphorylase... 

Fig. 2. Chemical structures of macrolide, lincosamide, and streptogramin type B antibiotics. Mac-rolide antibiotics (M) EM, CAM, AZM, HMR 3647, ABT-773, LM A5, RKM, TL, and YM133. Lin-cosamide antibiotics (L) LCM and CLDM. Streptogramin type B antibiotic (S) mikamycin B.

EM also has a motilin-like stimulating activity on gastrointestinal smooth muscles [39]. Therefore, the inhibitory effect on cytokine expression in human cells summarized here may be a third bioactivity of the macrolide antibiotic. We recently reported that some of these derivatives have inhibitory effect on IL-8 production by human airway epithelial cells [72], These analogues also showed inhibitory action on the activation of NFkB and AP-1 assessed by EMSA (M. Desaki etal., unpublished observations, January 2001). Characterization of the chemical structure responsible for its potential would be important to pursue and further investigation for the molecular mechanism would be necessary for a possible new type of anti-inflammatory agent. 

Looking back to the discovery of nalidixic acid almost 30 years ago, enormous efforts have been made and a huge number of analogs synthetized to improve overall properties. If one considers the relatively simple chemical structure of quinolones in comparison to other classes of antibacterials (macrolides, aminoglucosides, P-lactams), one can wonder if there is room for innovation or... 

Nowadays, antibiotics are primarily classified according to the mechanism of their action, with similarity of chemical structure as a secondary factor. Penicillin and its derivatives inhibit the formation of bacterial cell walls (Fig. 3.38). Cephalosporins have the same active mechanism. Other compounds are taken up into bacterial DNA to form unstable molecules (quinolones, metronidazole) or inhibit peptide synthesis (tetracychnes, aminoglycosides, macrolides). Some antibiotics (e.g. glycopeptides) exert a complex effect. 

Antibiotics differ widely in their polarities because then-chemical structures are very variable. They are synthesized by various living materials like bacterial strains (such as Streptomyces and Bacillus) and marine sponges. Oka et al., have gathered antibiotics purified by CCC from crude extract and fermentation broth. They have shown that CCC can be successfully applied to the separation of macrolides and of various other antibiotics, including various peptide antibiotics, which are strongly adsorbed to silanol groups on the silica gel used in the stationary... 

Figure 11.17 (a) Chemical structures of macrolide antibiotics (note that erythromycin, ETM, was analyzed as its anhydro form shown, (ETM-H2O)), but tylosin (TLS) was analyzed as the intact protonated molecule. Spiromycin (SPM) was used as the internal standard, (b) Multiple reaction monitoring (MRM) chromatograms of macrolides, each spiked at a concentration of 300ng.L before extraction from 100 mL of influent wastewater from a water reclamation plant. The MRM transitions used for quantitation are shown in each case (the precursor ion for Spiromycin I was the (M+2H) + ion, the others were (M+H)+ ions), and the total ion current (TIC) chromatogram is simply the sum of the three MRM traces. Reproduced from Yang, Anal. Bioanal Chem. 385, 623 (2006), with permission from Springer Science and Business Media. 

Although separation of polyene macrolide antibiotics is difficult, considerable progress has been achieved in their purification by HPLC and in the determination of (heir complex chemical structure by sensitive analytical methods, such as proton magnetic resonance, x-ray, and mass spectrometry. 

Figure 2 Chemical structure and building units of some polyene macrolide antibiotics. (Data from Refs, 2 and 7.) M, indicates mycosamine and Me a methyl group.

Figure 3 Chemical structures of the sugar moieties of polyene macrolide antibiotics.

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