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 £,/>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.