Design and synthesis of benzothiazole-based SLC-0111 analogues as new inhibitors for the cancer-associated carbonic anhydrase isoforms IX and XII.

In this work, different series of benzothiazole-based sulphonamides and carboxylic acids were developed as novel SLC-0111 analogues with the goal of generating potent carbonic anhydrase (CA) inhibitors. The adopted strategy involved replacing the 4-fluorophenyl tail in SLC-0111 with a benzothiazole motif that attached to the ureido linker to produce compounds and its regioisomers . In addition, the ureido spacer was elongated by methylene or ethylene groups to afford the counterparts and . In turn, the primary sulfamoyl zinc binding group (ZBG) was either substituted or replaced by carboxylic acid functionality in order to provide the secondary sulphonamide-based SLC-0111 analogues , and the carboxylic acid derivatives , respectively. All compounds ( and ) were tested for their ability to inhibit CA isoforms CA I, II, IX and XII. Additionally, the anticancer properties of the developed CAIs were evaluated.