Naslov
N'-substituted-2'-O, 3'-N-carbonimidoyl bridged macrolides : novel anti-inflammatory macrolides without antimicrobial activity

Autori
Bosnar, Martina ; Kragol, Goran ; Koštrun, Sanja ; Vujasinović, Ines ; Bošnjak, Berislav ; Mihaljević-Bencetić, Vlatka ; Ištuk-Marušić, Zorica ; Kapić, Samra ; Hrvačić, Boška ; Brajša, Karmen ; Tavčar, Branka ; Jelić, Dubravko ; Glojnarić, Ines ; Verbanac, Donatella ; Čulić, Ognjen ; Padovan, Jasna ; Alihodžić, Sulejman ; Haber-Eraković, Vesna ; Spaventi, Radan

Izvornik
Journal of medicinal chemistry (0022-2623) 55 (2012), 13; 6111-6123

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
antininflammatory; macrolides

Sažetak
Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti- inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O, 3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti- inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti- inflammatory therapeutics

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA