Dimeric sesquiterpene thioalkaloids with potent immunosuppressive activity from the rhizome of Nuphar pumilum:: Structural requirements of Nuphar alkaloids for immunosuppressive activity

被引：34

作者：

Matsuda, H ^{[1
]}

Shimoda, H ^{[1
]}

Yoshikawa, M ^{[1
]}

机构：

[1] Kyoto Pharmaceut Univ, Yamashina Ku, Kyoto 6078412, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2001年 / 9卷 / 04期

关键词：

D O I：

10.1016/S0968-0896(00)00327-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Potent immunosuppressive dimeric sesquiterpene thioalkaloids. 6-hydrotythiobinupharidine. 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B and 6'-hydroxythionuphlutine B. were isolated From the rhizome of Nuphar pumilum together with five inactive quinolizidine alkaloids. neothiobinupharidine, nupharidine, deoxynupharidinc, 7-epideoxynupharidine and nupharolutine. These dimeric sesquiterpene thioalkaloids were found to significantly inhibit anti-sheep erythrocyte plaque forming cell formation in mouse splenocytes at 1 muM. At this concentration. 6-hydroxythiobinupharidine. 6-hydroxythionuphlutine B and 6'-hydroxythionuphlutine B did not show cytotoxic effects to mouse splenocytes. and ,6,6'-dihydroxythiobinupharidine also showed only minor or minimal cytotoxicity. By comparison of the inhibitory activity of several Nuphar alkaloids on anti-sheep erythrocyte plaque forming cell formation, some structural requirements of Nuphar alkaloids for immunosuppressive activity were obtained. Namely, the 6- or 6'-hydroxyl group at the quinolizidine ring of dimeric sesquiterpene thioalkaloids is essential for the immunosuppressive effect. The number of hydroxyl groups appears to be related to the cytotoxicity, and the influence on splenocytes is greater with increasing numbers of hydroxyl groups. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1031 / 1035

页数：5

共 17 条

[11] 7-EPIDEOXYNUPHARIDINE FROM NUPHAR-LUTEUM SUBSP VARIEGATUM [J].

WONG, CF ;

LALONDE, RT .

PHYTOCHEMISTRY, 1970, 9 (03) :659-&

[12] STRUCTURE ON NUPHAROLUTINE, AN ALKALOID OF NUPHAR-LUTEUM [J].

WROBEL, JT ;

MACLEAN, DB ;

MARTIN, TI ;

BREAKMAN.C ;

IWANOW, A .

CANADIAN JOURNAL OF CHEMISTRY, 1972, 50 (12) :1831-&

[13] STRUCTURE OF THIOBINUPHARIDINE [J].

WROBEL, JT ;

BOBESZKO, B ;

MARTIN, TI ;

MACLEAN, DB ;

KRISHNAMACHARI, N ;

CALVO, C .

CANADIAN JOURNAL OF CHEMISTRY, 1973, 51 (17) :2810-2820

[14]

Yoshikawa M, 1997, CHEM PHARM BULL, V45, P756, DOI 10.1248/cpb.45.756

[15] Crude drugs from aquatic plants .6. On the alkaloid constituents of Chinese Nupharis Rhizoma, the dried rhizoma of Nuphar pumilum (TIMM.) DC. (Nymphaceae): Structures and rearragement reaction of thiohemiaminal type nuphar alkaloids [J].

Yoshikawa, M ;

Murakami, T ;

Wakao, S ;

Ishikado, A ;

Murakami, N ;

Yamahara, J ;

Matsuda, H .

HETEROCYCLES, 1997, 45 (09) :1815-1824

[16]

Yoshikawa M, 1999, CHEM PHARM BULL, V47, P524

[17] Crude drugs from aquatic plants. VII. Four new thiaspirane sulfoxide type nuphar alkaloids, nupharpumilamines A, B, C, and D, from Chinese Nupharis rhizoma, the rhizoma of Nuphar pumilum (Timm.) DC. (Nymphaceae) [J].