Naslov
Sterolides-a new class of potent anti-inflammatory compounds

Autori
Merćep, Mladen ; Tomašković, Linda ; Hrvačić, Boška ; Marković, Stribor ; Makaruha Stegić, Oresta ; Poljak, Višnja ; Komac, Marijana ; Šijan, Gordana ; Selmani, Selvira ; Ragač, Biserka ; Pešut, Anica ; Horvatinčić, Milka ; Bošnjak, Berislav ; Matijašić, Mario ; Vrančić, Mila ; Gjuračić, Krešimir ; Stanić, Barbara ; Stipaničić, Siniša ; Marković, Darko ; Ferenčić, Željko ; Mesić, Milan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The Inflammation Research Association, 12th International Conference - Abstracts. in: Inflammation Research. 53(Suppl 3):S, 2004 / - , 2004, 227-227

Skup
The Inflammation Research Association, 12th International Conference

Mjesto i datum
New York City (NY), Sjedinjene Američke Države, 03.10.2004. - 07.10.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
sterolides; antiinflammatory; asthma

Sažetak
Steroids are the most potent anti-inflammatory drugs and are a mainstay of asthma therapy. However, their use is associated with a number of unwanted side activities like growth retardation, suppression of hypothalamic-pituitary-adrenal axis (HPA), osteoporosis etc. Several strategies have been employed in development of anti-inflammatory steroids with reduced systemic side effects. Two main approaches have been: 1) increase of corticosteroids lipophilicity by esterifying the steroid hydroxyl groups, and 2) incorporation of metabolically labile functional groups at various positions of corticosteroids which undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation ("antedrug" or "soft" drug concept). We used a novel "sterolide" concept (steroid-macrolide conjugates) where we combined property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells (peripheral blood mononuclear cells, peritoneal and alveolar macrophages) with potent anti-inflammatory activity of classic steroids. These molecules accumulate in macrophage cell line Raw264.7 and lymphoid cell line Jurkat in vitro with greatly prolonged efflux time. Such sterolide molecules show excellent anti-inflammatory activity in several animal models with little or no systemic effects otherwise seen with standard steroids. Lead molecule is currently in the late preclinical development stage.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA