Synthesis And Biological Evaluation Of Cis-Combretastatin Analogs And Their Novel 1,2,3-Triazole Derivatives

Three cis-combretastatin analogs (8 - 10) and three novel 1,2,3-triazole derivatives (5 - 7) have been synthesized. The cis-combretastatins were prepared from selective hydrogenation of the corresponding alkyne. Reaction of the alkyne intermediates with benzyl azide via the [3+2] dipolar cycloaddition provided the 1,2,3-triazoles compounds. Removal of the benzyl group by catalytic hydrogenation afforded the desired triazoles 5 - 7 in good yields. The cytotoxicity of the target compounds against the growth of murine B16 melanoma cells was determined using a MTT-based assay. The results demonstrated the triazoles to have cytotoxicity comparable to the cis-combretastatins, with the IC50 values for compounds 7 and 10 as 56 mu M and 55 mu M, respectively.