Vanillin is one of the most important natural products, used as a starting material in the new drug design procedures. Starting from vanillin, we can prepare different chalcones, which are known for their pronounced pharmacological and biological activities. For this reason some chalcone analogues have been synthesized from the corresponding vanillin derivatives. Further reaction with hydrazine in formic acid or acetic acid yielded 20 new pyrazoline compounds with N-formyl and N-acetyl groups, respectively. All new compounds were well characterized by IR, ¹H and ¹³C NMR spectroscopy and physical data. In vitro DNA protective potential of selected compounds on hydroxyl and peroxyl radical-induced DNA damage was investigated. The results showed that the new synthesized compounds had expressed potential to prevent DNA damage.