Pharmaceuticals (Aug 2024)

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

  • Letizia Giampietro,
  • Beatrice Marinacci,
  • Alice Della Valle,
  • Ilaria D’Agostino,
  • Aldo Lauro,
  • Mattia Mori,
  • Simone Carradori,
  • Alessandra Ammazzalorso,
  • Barbara De Filippis,
  • Cristina Maccallini,
  • Andrea Angeli,
  • Clemente Capasso,
  • Santolo Francati,
  • Adriano Mollica,
  • Rossella Grande,
  • Claudiu T. Supuran

DOI
https://doi.org/10.3390/ph17081027
Journal volume & issue
Vol. 17, no. 8
p. 1027

Abstract

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

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