Bioactive cardenolides from the stems and twigs of Nerium oleander.
Four new cardenolide monoglycosides, cardenolides N-1 (1), N-2 (2), N-3 (3), and N-4 (4), were isolated from Nerium oleander, together with two known cardenolides, 5 and 12, and seven cardenolide monoglycosides, 6-11 and 13. The structures of compounds 1-4 were established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-13 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 1, 5, 6, and 11-13 were active at an IC50 value of less than 1 microM. The cytotoxicity of compounds 1-13 was evaluated against three human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 1, 4, 6, and 11-13 were active toward V-13 cells, and compounds 1, 11, and 12 were active toward HepG2 cells at IC50 values of less than 1 microM. Compounds 4, 5, 10, and 12 showed selective cell growth inhibitory activity toward V-13 tumor cells compared with that of parental normal WI-38 cells. The MDR-reversal activity of compounds 1-13 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 4, 9, and 10 showed significant effects on calcein accumulation, compound 4 showing stronger activity than that of verapamil.
Zhao
Ming
M
Graduate School of Science and Technology and Department of Chemistry and Chemical Engineering, Niigata University, Ikarashi, 2-8050, Niigata, 950-2181, Japan.
Bai
Liming
L
Wang
Liyan
L
Toki
Asami
A
Hasegawa
Toshiaki
T
Kikuchi
Midori
M
Abe
Mariko
M
Sakai
Jun-ichi
J
Hasegawa
Ryo
R
Bai
Yuhua
Y
Mitsui
Tomokazu
T
Ogura
Hirotsugu
H
Kataoka
Takao
T
Oka
Seiko
S
Tsushima
Hiroko
H
Kiuchi
Miwa
M
Hirose
Katutoshi
K
Tomida
Akihiro
A
Tsuruo
Takashi
T
Ando
Masayoshi
M
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002298:Cardenolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007564:Japan; D015394:Molecular Structure; D030007:Nerium / Q000737:chemistry*; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D002298:Cardenolides; D002301:Cardiac Glycosides; D018799:Intercellular Adhesion Molecule-1