Effects of ( + )-,(-)- And (±)-indenestrols A And B On Microtubule Polymerization

Taiko Oda, Yumiko Sakakibara, Yoshihiro Sato, Hiroyuki Hanzawa, Tadashi Hata

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Indenestrol A (IA) is a metabolite of diethylstilbestrol (DES), and indenestrol B (IB) is an analog of IA. IA was simply obtained from £,/>dienestrol in the presence of dilute sulfuric acid, and a mixture of IA and IB was formed by thermal cyclization of £,£-dienestrol. In order to elucidate the effects of optically active IA and IB on microtubule assembly, the IA and IB enantiomers were separated to >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)( + )-IA>(-)-IA>(-)-IB.

Original languageEnglish
Pages (from-to)588-592
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume40
Issue number3
DOIs
Publication statusPublished - 1992 Jan 1

Keywords

  • X-ray crystallography
  • absolute structure
  • indenestrol A
  • indenestrol B
  • inhibition
  • microtubule assembly
  • optical resolution

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

Fingerprint Dive into the research topics of 'Effects of ( + )-,(-)- And (±)-indenestrols A And B On Microtubule Polymerization'. Together they form a unique fingerprint.

Cite this