Bioactive pregnanes from Nerium oleander.
Three new pregnanes, 21-hydroxypregna-4,6-diene-3,12,20-trione (1), 20R-hydroxypregna-4,6-diene-3,12-dione (2), and 16beta,17beta-epoxy-12beta-hydroxypregna-4,6-diene-3,20-dione (3), were isolated from Nerium oleander, together with two known compounds, 12beta-hydroxypregna-4,6,16-triene-3,20-dione (neridienone A, 4) and 20S,21-dihydroxypregna-4,6-diene-3,12-dione (neridienone B, 5). The structures of compounds 1-3 were established on the basis of their spectroscopic data. The anti-inflammatory activity in vitro of compounds 2-4 was examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1), and compound 4 was active. The cytotoxic activity of compounds 1-5 was evaluated against four human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), human liver tumor cells (HepG2), and human lung carcinoma cells (A-549). Compound 4 showed significant cell growth inhibition of VA-13 and HepG2 cells. The MDR-reversal activity of compounds 1-5 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 1, 2, and 5 showed significant effects on calcein accumulation.
Bai
Liming
L
Graduate School of Science and Technology, Department of Chemistry and Chemical Engineering, Niigata University, Ikarashi, 2-8050, Niigata 950-2181, Japan.
Wang
Liyan
L
Zhao
Ming
M
Toki
Asami
A
Hasegawa
Toshiaki
T
Ogura
Hirotsugu
H
Kataoka
Takao
T
Hirose
Katutoshi
K
Sakai
Junichi
J
Bai
Jiao
J
Ando
Masayoshi
M
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D007564:Japan; D015394:Molecular Structure; D030007:Nerium / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D011278:Pregnanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism
C517577:16beta,17beta-epoxy-12beta-hydroxypregna-4,6-diene-3,20-dione; C517576:20R-hydroxypregna-4,6-diene-3,12-dione; C517575:21-hydroxypregna-4,6-diene-3,12,20-trione; D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D005452:Fluoresceins; D011278:Pregnanes; D018799:Intercellular Adhesion Molecule-1; C007740:fluorexon