Design, synthesis and in vivo activity of 9-(S)-dihydroerythromycin derivatives as potent anti-inflammatory agents

Mereu, Anna Rita; Moriggi, Ermanno; Napoletano, Mauro; Regazzoni, C.; Manfredini, Stefano; Mercurio, T.P.; Pellacini, F.

doi:10.1016/j.bmcl.2006.08.076

Cited by 15 publications

(8 citation statements)

References 13 publications

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“…These include (i) 9- ( S )-dihydroerythromycin derivatives which have been demonstrated to possess impressive anti-inflammatory activity in a murine model of phorbol ester-induced ear oedema [107], and (ii) more recently, the EM900 series of novel 12-membered, erythromycin-A-derived nonantibiotic macrolides [108]. EM900 was found to promote monocyte to macrophage differentiation, while suppressing activation of NF- κ B and IL-1 β , IL-8, and TNF- α gene expression in a human airway epithelial cell line (A549) activated with IL-1 β , as well as mucin ( muc5ac ) gene expression by HM3-muc5ac cells [58].…”

Section: Immunolidesmentioning

confidence: 99%

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Steel

Theron

Cockeran

et al. 2012

Mediators of Inflammation

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Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

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Section: Immunolidesmentioning

confidence: 99%

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Steel

Theron

Cockeran

et al. 2012

Mediators of Inflammation

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“…1 In our tentative preparation of de(N-methyl)-N-benzoyl-6-O-methyl erythromycin derivatives for the evaluation of their antiinflammatory activity, 2 we applied this methodology by treating de(N-methyl)-6-O-methyl erythromycin 1a with substituted benzoate A, B or C (1.2 equiv.) in the presence of potassium cyanide (1.0 equiv.)…”

mentioning

confidence: 99%

A novel type of N-formylation and related reactions of amines via cyanides and esters as formylating agents

Bao

Zhang

et al. 2008

Chem. Commun.

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“…Such compounds are completely devoid of antimicrobial effects but their anti‐inflammatory properties are enhanced. These results strongly suggest that macrolides could potentially be used as a new class of anti‐inflammatory agents (Mereu et al , 2006).…”

Section: Macrolide Antibioticsmentioning

confidence: 84%

“…Such compounds are completely devoid of antimicrobial effects but their anti-inflammatory properties are enhanced. These results strongly suggest that macrolides could potentially be used as a new class of anti-inflammatory agents (Mereu et al, 2006). Cao & Zhang (2007) recently published a review summarizing the synthesis pathway of glycosyl linked to macrolide antibiotics, the structural features of their glycosyltransferase, and glycosyl biofunction of macrolide antibiotics.…”

Section: Macrolide Antibioticsmentioning

confidence: 99%

Sweet antibiotics – the role of glycosidic residues in antibiotic and antitumor activity and their randomization

2008

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A large number of antibiotics are glycosides. In numerous cases the glycosidic residues are crucial to their activity; sometimes, glycosylation only improves their pharmacokinetic parameters. Recent developments in molecular glycobiology have improved our understanding of aglycone vs. glycoside activities and made it possible to develop new, more active or more effective glycodrugs based on these findings - a very illustrative recent example is vancomycin. The majority of attention has been devoted to glycosidic antibiotics including their past, present, and probably future position in antimicrobial therapy. The role of the glycosidic residue in the biological activity of glycosidic antibiotics, and the attendant targeting and antibiotic selectivity mediated by glycone and aglycone in antibiotics some antitumor agents is discussed here in detail. Chemical and enzymatic modifications of aglycones in antibiotics, including their synthesis, are demonstrated on various examples, with particular emphasis on the role of specific and mutant glycosyltransferases and glycorandomization in the preparation of these compounds. The last section of this review describes and explains the interactions of the glycone moiety of the antibiotics with DNA and especially the design and structure-activity relationship of glycosidic antibiotics, including their classification based on their aglycone and glycosidic moiety. The new enzymatic methodology 'glycorandomization' enabled the preparation of glycoside libraries and opened up new ways to prepare optimized or entirely novel glycoside antibiotics.

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Design, synthesis and in vivo activity of 9-(S)-dihydroerythromycin derivatives as potent anti-inflammatory agents

Cited by 15 publications

References 13 publications

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

A novel type of N-formylation and related reactions of amines via cyanides and esters as formylating agents

Sweet antibiotics – the role of glycosidic residues in antibiotic and antitumor activity and their randomization

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