title: Clionasterol: a potent inhibitor of complement component C1.
abstract: 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.
authors.forename: Fátima
authors.initials: F
authors.lastname: Cerqueira
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Watanadilok
authors.forename: Pichai
authors.initials: P
authors.lastname: Sonchaeng
authors.forename: Anake
authors.initials: A
authors.lastname: Kijjoa
authors.forename: Madalena
authors.initials: M
authors.lastname: Pinto
authors.forename: Henriette
authors.initials: H
authors.lastname: Quarles van Ufford
authors.forename: Burt
authors.initials: B
authors.lastname: Kroes
authors.forename: Cees
authors.initials: C
authors.lastname: Beukelman
authors.forename: Maria São José
authors.initials: MS
authors.lastname: Nascimento
mesh_terms: 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
chemical_list: D003169:Complement Inactivator Proteins; D012855:Sitosterols; C025473:gamma-sitosterol