Design, synthesis, biological evaluation and molecular modeling studies of 1-aryl-6-(3,4,5-trimethoxyphenyl)-3(Z)-hexen-1,5-diynes as a new class of potent antitumor agents

A series of novel enediyne-containing molecules, 1-aryl-6-(3,4,5- trimethoxyphenyl)-3(Z)-hexen-1,5-diynes, were synthesized and displayed significant IC₅₀ values of 10^-7 to 10^-6 M against various cancer cell lines. Of these compounds, 1-(2-pyridinyl)-6-(3,4,5- trimethoxyphenyl)-3(Z)-hexen-1,5-diyne (8) demonstrated the greatest growth inhibition activity. Compound 8 also arrested cancer cells in the G2/M phase and induced apoptosis via activation of Caspase-3. In addition to the G2/M block, compound 8 caused microtubule depolymerization at low concentrations and markedly decreased tumor size in xenographic studies.