The present work reports the synthesis of novel 5-Oxo-5,6,7,8-tetrahydroquinoline and 2,5-dioxo-5,6,7,8-tetrahydroquinoline derivatives containing enaminone system and bearing a sulfonamide moiety. The newly synthesized compounds were designed in compliance with the general pharmacophoric requirements for carbonic anhydrase inhibiting anticancer drugs, as this may play a role in their anticancer activity. Twelve of the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 5c, 7, 10, and 12c showed IC50 values (0.048, 0.040, 0.041, 0.044 mu M, respectively) comparable to that of the reference drug doxorubicin (IC50 = 0.04 mu M). On the other hand, compounds 12a, 12d, and 16b exhibited better activity than doxorubicin with an IC50 values (0.025, 0.036, 0.015 mu M, respectively).