2-Cyano-N'-[1-(2,5-dimethoxyphenyl)]ethylideneacetohydrazide 1 was obtained via reaction of cyanoacetic acid hydrazide with 2,5-dimethoxyacetophenone. A number of novel pyridines 2a-j, 3, 4, thiophenes 5-9 and thiazoles 10-12 were prepared by using the hydrazide-hydrazone derivative 1 as a starting material. The structure of the newly synthesized compounds was characterized by elemental analyses, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All the target compounds were subjected to in vitro antitumor activity against Ehrlich ascites carcinoma (EAC) cells. Compounds 2j and 6 showed a higher activity with IC(50) values (54.54, 61.57 μM), 8 when compared with a reference drug IC(50) value (68.99 μM), while compound 5 is nearly as active as doxorubicin (CAS 23214-92-8).