Erlotinib-Containing Benzenesulfonamides As Anti- Helicobacter Pylori Agents Through Carbonic Anhydrase Inhibition

Authors: Germán Benito; Ilaria D’Agostino; Simone Carradori; Marialuigia Fantacuzzi; Mariangela Agamennone; Valentina Puca; Rossella Grande; Clemente Capasso; Fabrizio Carta; Claudiu T Supuran doi:10.4155/fmc-2023-0208

Abstract

Aim: Development of dual-acting antibacterial agents containing Erlotinib, a recognized EGFR inhibitor used as an anticancer agent, with differently spaced benzenesulfonamide moieties known to bind and inhibit Helicobacter pylori carbonic anhydrase (HpCA) or the antiviral Zidovudine. Methods & materials:Through rational design, ten derivatives were obtained via a straightforward synthesis including a click chemistry reaction. Inhibitory activity against a panel of pathogenic carbonic anhydrases and antibacterial susceptibility of H. pylori ATCC 43504 were assessed. Docking studies on α-carbonic anhydrase enzymes and EGFR were conducted to gain insight into the binding mode of these compounds. Results & conclusion: Some compounds proved to be strong inhibitors of HpCA and showed good anti-H. pyloriactivity. Computational studies on the targeted enzymes shed light on the interaction hotspots.

Graphical Abstract

Keywords: 

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Author contributions

Conceptualization, F Carta, CT Supuran and S Carradori; data analysis, I D’Agostino, F Carta, R Grande and S Carradori; formal analysis, G Benito, I D’Agostino, M Fantacuzzi, M Agamennone, C Capasso and V Puca; writing and original draft preparation, G Benito, I D’Agostino, M Fantacuzzi and R Grande. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

The authors thank the Federal University of Paraíba and the Federal University for support and a fellowship to G Benito. This article is based on work from COST Action EURESTOP, CA21145, supported by COST (European Cooperation in Science and Technology) to S Carradori, R Grande, and I D’Agostino.

Financial disclosure

This work was supported by a grant from the Italian Ministry of University and Research for financial support under the FISR program, project FISR_04819 BacCAD to CT Supuran, C Capasso and S Carradori. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors declare no conflict of interest. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

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