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

• Main Authors: Letizia Giampietro (Author), Beatrice Marinacci (Author), Alice Della Valle (Author), Ilaria D'Agostino (Author), Aldo Lauro (Author), Mattia Mori (Author), Simone Carradori (Author), Alessandra Ammazzalorso (Author), Barbara De Filippis (Author), Cristina Maccallini (Author), Andrea Angeli (Author), Clemente Capasso (Author), Santolo Francati (Author), Adriano Mollica (Author), Rossella Grande (Author), Claudiu T. Supuran (Author)
• Format: Book
• Published: MDPI AG, 2024-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Research into novel anti-<i>Helicobacter pylori</i> 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 (<b>4a</b>-<b>j</b>) were performed to predict the putative binding mode to both HpCAs. Then, the antimicrobial activity versus <i>H. pylori</i> of the two series was also studied. The best-in-class compounds were found to be <b>4c</b> and <b>4e</b> among the primary azobenzenesulfonamides and <b>5c</b> and <b>5f</b> belonging to the secondary azobenzenesulfonamides series, showing themselves to exert a promising anti-<i>H. pylori</i> 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 <i>G. mellonella</i> larva in vivo model indicated a safe profile for <b>4c</b>,<b>e</b> and <b>5c</b>,<b>f</b>. The collected results warrant considering these azobenzenesulfonamides as an interesting starting point for the development of a new class of anti-<i>H. pylori</i> agents.

Item Description

10.3390/ph17081027
1424-8247