| Co-Investigator(Kenkyū-buntansha) |
WATANABE Kazuo Chiba Univ., FAculty of Pharm. Sci., Professor, 薬学部, 教授 (80019124)
YAMAZAKI Mikio Chiba Univ., Faculty of Pharm. SCI., Professor, 薬学部, 教授 (70089598)
NAKAGAWA Masao Chiba Univ., Faculty of Pharm. SCI., Assoc. Professor, 薬学部, 助教授 (40009171)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 1991: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1990: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1989: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Research Abstract |
1. Synthesis of beta-carbolines : Various eudistomins, marine beta-carboline alkaloids, were synthesized from N-hydroxytryptamine and cystine derivatives. First total synthesis of manzamine C, marine beta-carboline alkaloid, was completed from 1-methoxycarbonylmethyl-beta-carboline and azacycloundecene. The central ring system of manzamine A, pyrroloisoquinoline, was also synthesized. Over 40 compounds of beta-carboline derivatives prepared during these synthesis have been subjected to screening assay. Alkylation and asymmetric reduction of 3, 4-dihydro-beta-carboline have been investigated. Pictet-Spengler reaction with Lewis acid and chiral Lewis acids was investigated. Total synthesis of some marine ceramides were also completed. 2. Survey of active principles towards central nervous system in fungi : 1) Monoamine oxidase inhibitory (MAOI) activity was surveyed in fungi and lichens in vitro. MAOI activity of norsolorinic acid from Emericella and TL-1 from Talaromyces fungi was exami
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ned in vivo on anti-reserpine action. 2) Anti-endotheline-1 (or -norepinephrine) potency of several Bornean folk medicines was investigated by using smooth muscle of rat blood vessel to screen hypotensive principles. 3) HS-A, -B, and -C were isolated from Basidiomyceste, Hebeloma spoliatum, as active principle relaxing mouse small intestine like papaverine. 4) A new metabolie NFA was isolated as an inflammatory principle from an Ascomycete, Neosartorya fischeri, besides the tremorgenic principles, fumitremorgin A and B. 3. Pharmacological evaluation of cerebral insufficiency improving activity : To screen and evaluate cerebral insufficiency improving activities of beta-carbolines, several pharmacological studies were conducted ; 1) cholecystokinin (CKK) related activity, 2), calcium blocking activities, 3) potentiation of cholinergic action and 4) GABA related activities. In isolated preparations, some of beta-carbolines showed a specific antagonism to CCK, and others exerted a vasodialative action which may be related to calcium blockade. Most of compounds showing CCK antagonism in vitro also blocked the CCK-induced locomotor depression. These may be most promising as lead compound with therapeutic application. Beside the above trials, some studies were done to elucidate central mechanism of drug action. Less
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