Effects of (+)-, (-)- and (+/-)-indenestrols A and B on microtubule polymerization.
Indenestrol A (IA) is a metabolite of diethylstilbestrol (DES), and indenestrol B (IB) is an analog of IA. IA was simply obtained from E,E-dienestrol in the presence of dilute sulfuric acid, and a mixture of IA and IB was formed by thermal cyclization of E,E-dienestrol. In order to elucidate the effects of optically active IA and IB on microtubule assembly, the IA and IB enantiomers were separated to greater than 99% purity by high-pressure liquid chromatography using a chiral column. The di(4-bromobenzoate) of (-)-IB was analyzed by X-ray crystallography and its absolute structure was determined as C(3)-S. The (+)-, (-)-, and (+/-)-indenestrols A and B were shown to be inhibitors of microtubule assembly in vitro using microtubule proteins from porcine brain. (+/-)-IB is more active than (+/-)-IA, and the order of inhibitory activity of the enantiomers on microtubule assembly was (+)-IB greater than (+)-IA greater than (-)-IA greater than (-)-IB.
Oda
T
T
Kyoritsu College of Pharmacy, Shibakoen 1-chome, Minato-ku, Tokyo, Japan.
Sakakibara
Y
Y
Sato
Y
Y
Hanzawa
H
H
Hata
T
T
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004054:Diethylstilbestrol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D007192:Indenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008868:Microtubule Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects*; D011108:Polymers; D013237:Stereoisomerism; D013552:Swine; D014961:X-Ray Diffraction
D004968:Estrogens, Non-Steroidal; D007192:Indenes; D008868:Microtubule Proteins; D011108:Polymers; C047437:indenestrol; D004054:Diethylstilbestrol; C047501:indenestrol B