Synthesis of clitocybin A, B and C and their biological evaluation for antioxidant activities

Abstract

Clitocybin A, isolated from the culture broth of mushroom Clitocybe aurantiaca, showed various biological activities such as cell death inhibition effects, anti-wrinkle effects, aortic smooth muscle cell proliferation inhibition effects. In an effort to further develop this promising compound toward a potent antioxidant, we have modified the structure of clitocybin A by changing the number of free phenolic hydrogen in isoindolinone moiety. In this paper, clitocybin A and its analogues, clitocybin B and C were synthesized and their antioxidant activities were evaluated. Clitocybin A possessing two phenolic hydrogens in isoindolinone moiety of clitocybin A analogues showed more potent radical scavenging activity than clitocybin B possessing one phenolic hydrogen. In inhibition of cellular DNA damage in H2O2treated cells, clitocybin C lacking free phenolic hydrogen in isoindolinone moiety showed more potent activity than clitocybin A possessing two phenolic hydrogens.Among the tested compounds, clitocybin A only showed dose-dependently HNE inhibitory activity with an IC50 value of 78.8 uM. The presence of free phenolic hydrogens inisoindolinone moiety of clitocybin A analogues plays an important role in antioxidant activities.