Clionasterol: a potent inhibitor of complement component C1.
Clionasterol (1a), clionasterol monoacetate (1b) and 5alpha,8alpha-epidioxy-24alpha-ethylcholest-6-en-3-ol (2), isolated from the marine sponge Xestospongia exigua, and beta-sitosterol (3) were tested for their influence on the classical (CP) and alternative (AP) pathways of activation of the human complement system in vitro. All the sterols inhibited the CP in a dose-dependent manner but no detectable effect was observed in the AP even at concentrations of 400 microM. Clionasterol was found to be a potent inhibitor of CP (IC50 = 4.1 microM) being ten-fold more active than beta-sitosterol. The presence of the epidioxy group on C-5 and C-8 of compound 2 caused a pronounced decrease of the inhibitory effect. Mechanistic studies on the anticomplementary effect of clionasterol revealed that it interferes with the complement component C1.
Cerqueira
Fátima
F
Watanadilok
Rawiwan
R
Sonchaeng
Pichai
P
Kijjoa
Anake
A
Pinto
Madalena
M
Quarles van Ufford
Henriette
H
Kroes
Burt
B
Beukelman
Cees
C
Nascimento
Maria São José
MS
D000818:Animals; D003169:Complement Inactivator Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D011161:Porifera; D012855:Sitosterols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D003169:Complement Inactivator Proteins; D012855:Sitosterols; C025473:gamma-sitosterol