Effects of synthetic estrogens, (R,R)-(+)-, (S,S)-(-)-, dl- and meso-hexestrol stereoisomers on microtubule assembly.

We previously reported on the inhibition of microtubule polymerization and the formation of ribbon structures by synthetic estrogens [Sato et al., J Biochem 101: 1247-1252, 1987]. The present investigation aimed to analyse these effects in vitro on stereochemical point of view, using hexestrol isomers ((R,R)-(+)-hexestrol, (S,S)-(-)-hexestrol and meso-hexestrol) and dl-hexestrol. Among hexestrols, dl-hexestrol showed the highest activity in ribbon formation from microtubule proteins at 100 microM. On the other hand, meso-hexestrol was distinguished from others by inhibition of microtubule assembly and formation of a large amount of aggregates from purified tubulin in the presence of MgCl2 and DMSO. These results were discussed with physico-chemical properties of hexestrols, e.g. absolute configurations as well as circular dichroism spectra and solid state carbon-13 nuclear magnetic resonance spectra.