Inhibition of carbonic anhydrase isozymes has been found to have a role in the treatment of cancer. Several sulfonamide compounds bearing an aromatic or a heteroaromatic ring were found to posses potent carbonic anhydrase inhibitory activity and so can be used in the treatment of several types of cancer. In this paper, we present the synthesis of some novel quinoline 7-13, 21-26, 28 and pyrimidoquinoline 14-18, 20, 27 derivatives having a sulfonamide moiety. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Several compounds showed interesting cytotoxic activities when compared with the used reference drug. In addition, docking of the synthesized compounds into carbonic anhydrase isozyme II (CA II) active site was performed in order to give a suggestion about the proposed mechanism of action.