4-Acetyl-1,2,3-triazole derivative reacts with cyanoacethydrazide in ethanol to give 2-cyano-N'-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)acetohydrazide (3). The latter was submitted to react by condensation with benzaldehyde and its derivatives in ethanol in the presence of piperidine to give the corresponding arylidene derivatives Compound 5a reacts with a variety of heteroamines to give the corresponding annulated azolopyrimidine compounds. Additionally, 2-cyano-N-(substituted-1,2,3,-triazole-4-yl)ethylidene)acetohydrazide reacts with 2-bis(methylthio)methylene malononitrile in ethanol and in the presence of potassium hydroxide to give Triazolylhydrazonopyridine deravative. Treatment of the latter compound with hydrazine hydratein ethanol under reflux led to formation of pyrazolopyridine derivative. The structure of all the newly synthesized compounds were fully identified using spectroscopic and elemental analysis. Moreover, the newly synthesized compounds were screened for their antiproliferative potential in vitro towards different human cell lines, including: colon (LoVo), and liver (HEPG2) and breast (MCF7) cancer cell lines. Results revealed that compounds 5d, 5b, 5c and 5f were the most potent against tested cancer cell lines. Moreover, compound 5d was chosen for a further drug delivery study through using chitosan and PVA polymer film as drug carrier. This drug delivery system was used for in vitro anticancer evaluation and genotoxic investigation compared to Doxorubicin. colon (LoVo) cells were treated with various concentrations from the selected compound 5d loaded in CS/PVA drug delivery in comparison to doxorubicin to evaluate its anticancer activity.