Toward developing anticancer agents, heterocycle-based carboxymethyl cellulose conjugates have been synthesized. 2-Cyano-N'-(aryl/heteroarylethylidene)acetohydrazides and ethyl 2-cyano-3-(heteryl)acrylates were utilized as precursors for the synthesis of pyridine-based compounds. The chemical structures of the synthesized derivatives were characterized using various spectroscopic techniques, including H-, C-NMR, Fourier transform infrared spectroscopy (FTIR), as well as scanning electron microscopy (SEM).The anticancer effects of compounds on HCT-116, MCF-7, PC3 and A549 cancer cell lines were investigated and their cytotoxicity against RPE-1 normal cells was estimated to determine their safety. Compounds 4b and 7c exhibit high selectivity toward cancer cells while maintaining a strong safety margin for normal cells. The results demonstrated that the novel heterocycle-based carboxymethyl cellulose conjugates are promising and can be further evaluated as a potential therapeutic agent.