Synthesis and X-ray structure of potent anticancer 4-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)isoxazole

The three-step synthesis of potent anticancer 4-(4-methoxy- phenyl)-3-(3,4,5-trimethoxyphenyl)isoxazole starting from 1,2,3-trimethoxy-5-(nitromethyl)benzene and anisaldehyde was developed. In phenotypic sea urchin embryo assay, this compound exhibited antimitotic antitubulin activity comparable to that of the natural cytostatic combretastatin A4 (CA4). The title isoxazole inhibited in vitro growth of A549 human lung cancer cells and PC-3 human prostate cancer cells with IC₅₀ values of 8 and 6 nm, respectively, exceeding the effect of CA4.