Activity-guided isolation of steroidal alkaloid antiestrogen-binding site inhibitors from Pachysandra procumbens.
Four novel steroidal alkaloids, (+)-(20S)-20-(dimethylamino)-3-(3'alpha-isopropyl)-lactam-5alpha-+ ++preg n-2-en-4-one (1), (+)-(20S)-20-(dimethylamino)-16alpha-hydroxy-3-(3'alpha-isopropyl) -la ctam-5alpha-pregn-2-en-4-one (2), (+)-(20S)-3-(benzoylamino)-20-(dimethylamino)-5alpha-pregn-2-en-++ +4beta -yl acetate (3), and (+)-(20S)-2alpha-hydroxy-20-(dimethylamino)-3beta-phthalimido-5 alpha- pregnan-4beta-yl acetate (4), as well as five known compounds, (-)-pachyaximine A (5), (+)-spiropachysine (6), (+)-axillaridine A (7), (+)-epipachysamine D (8), and (+)-pachysamine B (9), were isolated from Pachysandra procumbens, using a bioassay-guided fractionation based on inhibition of 3H-tamoxifen binding at the antiestrogen binding site (AEBS). Compounds 1-7 and 9 demonstrated significant activity as AEBS-inhibitory agents, and compounds 3, 5 and 9 were found to potentiate significantly the antiestrogenic effect mediated by tamoxifen in cultured Ishikawa cells. The structure elucidation of compounds 1-4 was carried out by spectral data interpretation.
Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
L C
LC
Chang
K P
KP
Bhat
E
E
Pisha
E J
EJ
Kennelly
H H
HH
Fong
J M
JM
Pezzuto
A D
AD
Kinghorn
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004965:Estrogen Antagonists / Q000378:metabolism*; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D010840:Phytosterols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010944:Plants / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000470:Alkaloids; D004965:Estrogen Antagonists; D010840:Phytosterols; D013629:Tamoxifen