| Co-Investigator(Kenkyū-buntansha) |
KAMISAKO Wasuke Mukogawa Woman's Univ. Fac. Pharm. Sci. Prof., 薬学部, 教授 (60085280)
TANAKA Shigeo Kyoto Univ., Fac. Pharm. Sci. Assist., 薬学部, 助手 (30115878)
FUKUI Hiroshi Kyoto Univ., Fac. Pharm. Sci. As. Prof., 薬学部, 助教授 (80026575)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1989: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Research Abstract |
We showed earlier that cultured cells of Luffa cylindrica produce a large amount of a unique pentacyclic triterpenoid, bryonolic acid, having antiallergic activities. In the present study, we have prepared eight derivatives of bryonolic acid by chemical synthesis to examine structure-activity relation ship in regard to their inhibitory potential against type I-allergy in mice. The results of animal experiments have shown that the antiallergic activity was influenced by the number and position of double bonds in the triterpene skeleton. The activity was increased significantly by reducing the carboxyl group at the C_<29> position into alcohol. However, the most dramatic increase in activity was shown by succinate and phthalate esters of bryonolic acid, their activity being 6 to 11 times as high as that of the latter and 3 to 5 times as high as TRANILAST, a commercially available antiallergic drug. These results indicate the importance of the carboxyl group, in particular, of its position and moiety.
Bryonolic acid succinate-2K was found to exhibit a stronger inhibitory activity against passive cutaneous anaphylaxis than bryonolic acid phthalate-2K both in either oral or intraperitoneal administration to mice. Furthermore, this compound proved to be effective against the allergy of the types III and IV as well as against that of the type I by oral administration, showing a wide antiallergic spectrum. In addition, this compound showed no apparent acute toxicyty to mice, causing no death even at a high dose of 4g/kg body wt (p. o.).
In view of the results of pharmacological experiments as well as of culture experiments that Luffa cylindrica cell cultures are capable of producing bryonolic acid at a high yield (ca. 4% of dry weight of cells), its esterified derivative, bryonolic acid succinate, is considered to be a hopeful new antiallergic agent.
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