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.
Chang
L C
LC
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.
Bhat
K P
KP
Pisha
E
E
Kennelly
E J
EJ
Fong
H H
HH
Pezzuto
J M
JM
Kinghorn
A D
AD
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