Inhibitors of kinesin Eg5: antiproliferative activity of monastrol analogues against human glioblastoma cells

摘要: The inhibition of kinesin Eg5 by small molecules such as monastrol is currently evaluated an approach to develop a novel class antiproliferative drugs for the treatment malignant tumours. Therefore, we studied effects new analogues enastron, dimethylenastron and vasastrol VS-83 on proliferation human glioblastoma cells in kinetic crystal violet assay. Compared monastrol, cell cycle specific compounds showed at least one order magnitude higher anti proliferative activity against U-87 MG, U-118 U-373 MG cells. were neither inactivated hydrolysis nor binding serum proteins. Moreover, demonstrated characteristic monoaster formation after incubation with confocal laser scanning microscopy. We also that arrangement beta-actin tubulin, vital components cyto-skeleton mitotic quiescent cells, not affected compounds. Due necessity overcoming blood-brain barrier brain tumours, investigated if are modulators or substrates p-glycoprotein (p-gp) 170 flow cytometric calcein-AM efflux tested no modulating p-gp function. With respect primary secondary CNS results our experiments suggest represent interesting potential anticancer drugs, predicted be less neurotoxic comparison classical tubulin inhibitors.