AI Article Synopsis
- Clionasterol, clionasterol monoacetate, and other sterols from the marine sponge Xestospongia exigua were tested for their effects on the human complement system.
- All sterols showed a dose-dependent inhibition of the classical pathway (CP) but had no effect on the alternative pathway (AP) at high concentrations.
- Clionasterol was identified as the most potent inhibitor of CP, effectively targeting complement component C1, while the presence of an epidioxy group in another compound reduced its inhibitory effectiveness.
Article 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.
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