Fluorenone-azomethines a novel class of microtubule inhibitors that specifically affect cell proliferation

Summary The effects of various azomethine derivatives on microtubule ( MT ) assembly in vitro as well as on cell proliferation cell shape and the cytoskeleton of some cultured murine cell lines were studied. 3 of them the a-diphenylene-N-{p-[bis-((β-hydroxyethyl)-amino]-phenyl}-nitrone ( DHPN ) α-diphenylene-N-{γ-[N-(hydroxyethyl)-N-(y-hydroxypropyl)-amino]-phenyl}-nitrone and α-diphenylene-N-(p-diethylaminophenyl)-nitrone strongly inhibit the assembly of microtubules ( MTs ) in vitro (50 % inhibition at 4 to 7 µmol/1). The same compounds are also able to disrupt preformed microtubules. Moreover they were found to inhibit proliferation of leukaemia L 1210 melanoma B16 K fibroblast L 929 and embryo fibroblast cells down to 1 to 10 [moUl completely. Immunofluorescence microscopy revealed that DHPN used as a representative of the active azomethines causes a reversible destruction of the microtubule part of the cytoskeleton. Apparantly resulting from microtubule disruption the intermediate filament system collapsed whereas the microfilament system remained unaffected. The results indicate that the antiproliferative action of the azomethines is based at least partially on their ability to attack microtubules.