Corticoid 활성물질의 개발을 위한 기초연구(I) 11-Oxo-oleanolic Acid 및 11-Oxo-hederagenin의 Corticoid-5beta-reductase에 대한 조해효과

Studies on Triterpenoid Corticomimetics (I) Inhibition of Corticoid-5beta-reductase by 11-Oxo-oleanolic Acid and 11-Oxo-hederagenin

Derivation of triterpenoids and then the screening for corticomimetics among them is our primary interest. C11-oxo-triterprenoids except glycyrrhetinic acid are rarely found in the plant kingdom. Based on the facts that C3 and C11-Oxo-group are essential for the corticoid-like-activity through its competitive inhibition on the corticoid-5beta-reductase, it was attempted to produce artificial inhibitor on the enzyme by introducing C11-oxo group to the triterpenoids of oleanene series such as oleanolic acid and hederagenin. We could obtain the C11-oxo-oleanolic acid m.p. 264~6o, uv lamdamax 249 and C11-oxo-hederagenin amorp. uv lamdamax 251 by acetylation, CrO3-oxid., and deacetylation. Glycyrrhetinic acid, a natural 11-oxo-compound and the other 11-oxo-derivatives of oleanolic acid and hederagenin were compared in their inhibitory activity on the corticoid-5beta-reductase. The inhibitory activity of those compound were decreased in the order of C11-oxo-oleanolic acid, C11-oxo-hederagenin, glycyrrhetinic acid. This suggests more strong corticomimetic activity of those artificially derived C11-oxo-oleanolic acid and C11-oxo-hederagenin. Their Ki value were 4.6 X 10-4M and 5.8 X 10-4M respectively.