Nuphar alkaloids with immediately apoptosis-inducing activity from Nuphar pumilum and their structural requirements for the activity.
The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar pumilum showed cytotoxic effects on human leukemia cell (U937), mouse melanoma cell (B16F10), and human fibroblast (HT1080). Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial cytotoxic activity at a concentration of 10 microM, but dimeric sesquiterpene thioalkaloids lacking the 6-hydroxyl group (thiobinupharidine, thionuphlutine B, 6'-hydroxythionuphlutine B, neothiobinupharidine, thionuphlutine B beta-sulfoxide, and neothiobinupharidine beta-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, 7-epideoxynupharidine, and nupharolutine) showed weak activity. Next, apoptosis-inducing activity of a principal active constituent, 6-hydroxythiobinupharidine, on U937 was examined using morphological observation and DNA fragmentation assay (TUNEL method). Apoptosis of U937 was immediately observed within 1 h after treatment of 6-hydroxythiobinupharidine at 2.5-10 microM.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Yoshida
Kazutoshi
K
Miyagawa
Katsutoshi
K
Nemoto
Yumiko
Y
Asao
Yasunobu
Y
Yoshikawa
Masayuki
M
D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D007938:Leukemia / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D031654:Nuphar; D027343:Rhizome; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000970:Antineoplastic Agents; D012717:Sesquiterpenes