Clionasterol: A Potent Inhibitor of Complement Component C1

Abstract

Clionasterol (1a), clionasterol monoacetate (1b) and 5α,8α-epidioxy-24α-ethylcholest-6-en-3-ol (2), isolated from the marine sponge Xestospongia exigua, and β-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 μM. Clionasterol was found to be a potent inhibitor of CP (IC₅₀ = 4.1 μM) being ten-fold more active than β-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.

References

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