INTERACTION OF GEIPARVARIN AND RELATED-COMPOUNDS WITH PURIFIED MICROTUBULAR PROTEIN

Geiparvarin is an antiproliferative compound whose mechanism of action has not yet been identified. We have investigated the biochemical act ion on purified microtubular protein, as well as on tubulin, of geipar varin and of some derivatives resulting from its conjugation with two synthetic oestrogens, diethylstilboestrol and meso-hexoestrol, in comp arison with the antimicrotubular action of the reference oestrogens. G eiparvarin and derivatives did not inhibit colchicine binding to tubul in nor did they significantly influence GTP-induced polymerization. On the contrary, they effectively counteracted the stimulating effect of taxol on microtubule formation, both in the presence and in the absen ce of microtubule associated proteins. A competitive inhibition mechan ism at the taxol binding site of tubulin may thus be proposed to expla in the antimicrotubular action of geiparvarin.