Cytotoxic monoaryl furazanopyrazines with microtubule destabilizing activity in the sea urchin embryo model

Biological activity of monoaryl furazanopyrazines (FPs), known as high-energy molecules, is scarcely explored. A series of monoaryl FPs was synthesized by condensation of arylglyoxals with diaminofurazane. The targeted compounds at low micromolar concentrations inhibited growth of human cancer cells in NCI60 screen. Further evaluation using a sea urchin embryo model revealed that antiproliferative activity of monoaryl FPs could be associated with targeting tubulin and microtubule destabilization, systemic (nonspecific) toxicity, or both. Introduction of hydroxy group into pyrazine ring of monoaryl FPs yielded inactive molecules.