Several novel pyrazole 10–16 and pyrimidine 17–19 derivatives bearing Sulfonamide moieties were synthesized in order to study their antitumor activity. The synthesized compounds were characterized by elemental analysis, IR, 1 H-NMR, and mass spectral data, then screened as antitumor agents against human tumor liver and breast cell lines (HEPG2 and MCF7). All the tested compounds were more potent than the reference drug doxorubicin on human liver (HEPG2) cell line, while on human breast cancer (MCF7) cell line, they were less potent than the reference drug. Additionally, some of the synthesized compounds were evaluated for their ability to enhance the cell killing effect of c-radiation.