A series of novel 3,4,5-trimethoxycinnamamide-tethered 1,2,3-triazole derivatives were prepared by the click reaction of (E)-N-(prop-2-yn-1-yl)-3-(3,4,5-trimethoxyphenyl) acrylamide with different aryl azides. The synthesized compounds were characterized by 1H and 13C NMR and mass spectra and elemental analyses and were screened for their in vitro anticancer activity against MCF-7 and A549 cell lines by using MTT assay. Most of the tested compounds showed prominent activity against both cancer cell lines. [ABSTRACT FROM AUTHOR]