This study aims to synthesize a novel series of nicotinonitriles incorporating pyrazole, oxadiazole, isoindoline, thiadiazole, and thiazolidinone moieties (compounds 4-11). The synthesis utilizes 2-((3-cyano-4-(4-fluorophenyl)-6-(naphthalen-2-yl)pyridin-2-yloxy)acetohydrazide (3) as a key starting material to enhance potential anticancer activity. The molecular structures of compounds 4-11 were elucidated using various spectroscopic techniques and elemental analysis. The synthesized compounds were screened for cytotoxic activity against human cancer cell lines, including MCF-7 (human Caucasian breast adenocarcinoma), MDA-MB-231 (breast ductal carcinoma), and PC-3 (prostate cancer), using an MTT assay with doxorubicin as a reference drug. Among the tested compounds, 4, 6b, and 7 exhibited the most promising cytotoxic activity, with IC