Anti-complement activity in a series of substituted 2-aryl-1,3-indandiones; absence of correlation with the anti-carrageenan oedema effects.
It was found that a number of substituted 2-phenyl-1,3-indandiones possesses a considerable inhibitory effect on the classical pathway of complement. Furthermore it appeared that in this series a reasonable correlation (r = 0.86) exists between this anti-complement effect and the inhibition of the prostaglandine biosynthesis. A quantitative structure-activity relation study revealed that both the electronic sigma parameter of the substituent involved and the lipophilicity of the corresponding compound are important for anti-complement activity. Mainly the C5 step in the complement process is inhibited by these compounds. The complement-inhibiting phenylindandiones also inhibit the alternative pathway. This effect may also be due to an inhibition of C5, as C5 is common to both pathways. Remarkably, the 2-(3,5-dichlorophenyl)-1,3-indandione, which is most active in the anti-complement test, showed no reduction of the carrageenan-induced oedema in the rat after both oral and local application. Possibly the absence of this anti-inflammatory effect is caused by the pharmacokinetic profile of the compound.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000037:antagonists & inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006461:Hemolysis / Q000187:drug effects; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology; D007192:Indenes / Q000138:chemical synthesis*; D011817:Rabbits
D000893:Anti-Inflammatory Agents; D003169:Complement Inactivator Proteins; D007189:Indans; D007192:Indenes; D002351:Carrageenan