Naslov
Protuupalna aktivnost novih dibenzo[e, h]azulenskih spojeva za tretiranje reumatoidnog artritisa
(Antiinflammatory activity of novel dibenzo[e, h]azulene compounds for the treatment of rheumatoid arthritis)

Autori
Stanić, Barbara ; Pešić, Dijana ; Ozimec Landek, Ivana ; Trojko, Rudolf ; Rupčić, Renata ; Modrić, Marina ; Mesić, Milan ; Merćep, Mladen

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

Izvornik
Inflammation Research, Supplement 2 / - , 2005

Skup
Inflammation

Mjesto i datum
Melbourne, Australija, 20.08.2005. - 24.08.2005

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
TNFalpha; dibenzo[e; h]azulenes; antiinflammatory activity

Sažetak
Purpose: Discovery of effective, orally acting, small molecular weight inhibitors of TNF-a production for the treatment of RA and other diseases in which TNF-a plays important role in pathogenesis. Methods: Synthesis of new dibenzo[e, h]azulenes and their testing in several inflammatory models (LPS induced TNF-a production, LPS induced shock, writhing and hot plate models of analgesia, carrageenan induced paw edema and adjuvant induced arthritis model). Results: Members of different classes of dibenzo[e, h]azulenes inhibit TNF-a production in vitro in low micromolar range. Selected compounds administered per-orally showed potent inhibition of LPS induced TNF-a secretion in vivo. They also exhibit excellent activity in different acute inflammatory models such as LPS induced shock and carrageenan induced paw edema. Activity of some dibenzo[e, h]azulene compounds was confirmed in adjuvant induced arthritis model in rats when they had been dosed perorally in established phase of the disease. Effects included not only decrease in degree of inflammation but also remarkable attenuation of degenerative processes reversing histopathological changes that are characteristic for RA. In addition, these compounds have analgesic activity comparable to that of acetylsalicylic acid when tested in the writhing model of analgesia. Conclusions: Good toxicology profile, lack of genotoxicity and good safety profile indicate that dibenzo[e, h]azulene class of orally available TNF-a inhibitors could bring disease modifying activity and symptomatic relief to RA patients.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA