Thirteen novel benzazole derivatives were synthesized as possible anticancer agents. The first intermediate 1,3-benzothiazol-2-ylacetonitrile (2) was synthesized via cyclodeamination reaction of o-aminothiophenol (1) with malononitrile. Also, the second intermediate 5,6-dimethyl-1H-benzimidazol-2-ylacetonitrile (10) was afforded via cyclocondensation reaction between 4,5-dimethyl-1,2-phenylenediamine (9) and ethylcyanoacetate. Nucleophilic reaction of benzimidazolyl NH of compound (10) with ethylcyanoacetate afforded benzimidazolyl-3-oxopropanenitrile (11). On the other hand, methylenation of CH(2) function of compound (10) with dimethylformamide/dimethylacetal afforded benzimidazolylprop-2-enenitrile 12. The synthesis of benzothiazoylpyridines 5a,b and 8a,b as well as benzimidazolylpyridines, 14a,b and 17a-d was carried out through Michael addition of compounds 2 or 10 with arylidenemalononitriles 3a,b and 4a-d. The combination of pharmacophoric anticancer moieties, pyridine and benzazoles was the base on which target compounds 5a,b, 8a,b, 14a,b and 17a-d were designed. Among the synthesized compounds, four derivatives 10 and 17b-d were selected by National Cancer Institute (NCI), USA to be screened for their anticancer activity at a single high dose (10(-5) M) against a panel of 60 cancer cell lines. Compound 17b 4-[p-chlorophenyl]pyridine and 17d 4-[p- methoxyphenyl] pyridine exhibited a broad and moderate antitumor activity against 41 tumor cell lines belonging to the nine subpanels employed and are selected for further evaluation at five dose level screening.