It has been reported that aryl/heteroaryl sulfonamide compounds may act as anticancer agents through a variety of mechanisms and the most prominent of these mechanisms is through the inhibition of carbonic anhydrase isozymes. The present work reports the possible utility of 4-(cyclohexenylamino)benzenesulfonamide in the synthesis of some novel 4-(quinolin-1-yl)benzenesulfonamide derivatives 6a-u. The structures of these compounds were confirmed by elemental analyses, IR, (1)H NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Some compounds showed interesting in vitro anticancer activities when compared with doxorubicin as a 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.