Azobenzenesulfonamide Carbonic Anhydrase Inhibitors as New Weapons to Fight Helicobacter pylori : Synthesis, Bioactivity Evaluation, In Vivo Toxicity, and Computational Studies

Research into novel anti- agents represents an important approach for the identification of new treatments for chronic gastritis and peptic ulcers, which are associated with a high risk of developing gastric carcinoma. In this respect, two series of azobenzenesulfonamides were designed, synthesized, and tested against a large panel of human and bacterial CAs to evaluate their inhibitory activity. In addition, computational studies of the novel primary benzenesulfonamides ( - ) were performed to predict the putative binding mode to both HpCAs. Then, the antimicrobial activity versus of the two series was also studied. The best-in-class compounds were found to be and among the primary azobenzenesulfonamides and and belonging to the secondary azobenzenesulfonamides series, showing themselves to exert a promising anti- activity, with MIC values of 4-8 μg/mL and MBCs between 4 and 16 μg/mL. Moreover, the evaluation of their toxicity on a larva in vivo model indicated a safe profile for , and , . The collected results warrant considering these azobenzenesulfonamides as an interesting starting point for the development of a new class of anti- agents.