A convenient synthesis of cis-restricted combretastatin analogues with pyrazole and isoxazole cores

A series of combretastatin analogues, diarylpyrazoles and diarylisoxazoles, have been synthesized and evaluated for their antimitotic tubulin-binding activity using the phenotypic sea urchin (Paracentrotus lividus) embryo assay. One pyrazole analogue and four isoxazole analogues have been identified as potent antimitotic agents comparable with combretastatins A-2 and A-4, with the lowest observable effective concentration of 1–10nmoldm⁻³ for cleavage alteration of the test embryos.