2-(4-methyl-1-piperazinylmethyl) acrylophenone dihydrochloride: a new antimicrotubular drug.

With the relation between chemical structure and pharmacological activity as a guide, we have been for some time synthetizing a wide range of beta-amino-ketone derivatives. One of them, 2-(4-methyl-1-piperazinylmethyl) acrylophenone, MPMAP, possesses antimicrotubular activities. This product inhibits 50% of the microtubule polymerization at a 3.10(-5) M concentration. It does not prevent tubulin paracrystal formation induced by vinblastine, and binding experiments reveal that this product is a weak inhibitor of colchicine binding. The structure of this compound is different from the other antimicrotubular agents and has the advantage of being far less complex, highly soluble and easy to synthesize. Thus, this product and related compounds should be a new tool for the study of antimicrotubular activities and tubulin assembly.