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

Abstract 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 μM. 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 MgCl 2 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.