Discovery of New Selenoureido Analogues of 4-(4-Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase Inhibitors

Abstract

A series of benzenesulfonamides bearing selenourea moieties was obtained considering the ureido-sulfonamide <b>SLC-0111</b>, in Phase I clinical trials as antitumor agent, as a lead molecule. All compounds showed interesting inhibition potencies against the physiologically relevant human (h) carbonic anhydrase (hCAs, EC 4.2.1.1) isoforms I, II, IV, and IX. The most flexible analogues in the series <b>14</b>-<b>19</b> showed low nanomolar inhibition constants against hCA I, II, and IX. We assessed selected compounds on the <i>in vitro</i> antioxidant properties and binding modes and evaluated <i>ex vivo</i> human prostate (PC3), breast (MDA-MB-231), and colon-rectal (HT-29) cancer cell lines both in normoxic and hypoxic conditions.