Docking of T6361 Analogues as Potential Inhibitors of E.coli MurA Followed by ADME-Toxicity Study

Ilham Boulhissa; Hanane Boucherit; Abdelouahab Chikhi; Abderrahmane Bensegueni

doi:10.2174/0115701638244582231025110143

Docking of T6361 Analogues as Potential Inhibitors of E.coli MurA Followed by ADME-Toxicity Study

Curr Drug Discov Technol. 2023 Oct 30. doi: 10.2174/0115701638244582231025110143. Online ahead of print.

Authors

Ilham Boulhissa¹, Hanane Boucherit^{1

2}, Abdelouahab Chikhi¹, Abderrahmane Bensegueni¹

Affiliations

¹ Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, University of Mentouri Brothers Constantine 1, Constantine, Algeria.
² Abdelhafid Boussouf University Center, Mila, Algeria.

PMID: 37929742
DOI: 10.2174/0115701638244582231025110143

Abstract

Background: Developing more potent antibacterial agents is one of the most important tasks of scientists in the health field due to the problem of antibiotic resistance. Among the antibiotic targets, we mention MurA (UDP-N-Acetylglucosamine Enolpyruvyl Transferase), which is a key enzyme of peptidoglycan biosynthesis of the bacterial cell wall.

Objective: Our objective was to search for new inhibitors of the bacterial enzyme MurA by docking the analogues of its inhibitor T6361, a derivative of 5-sulfonoxy-anthranilic acid.

Methods: 990 analogues of T6361 were docked in the first binding site of E.coli MurA (open form) using the FlexX program, and the ADME-Toxicity profile of the best ones was evaluated by SwissADME and PreADMET web servers.

Results: Docking results revealed two T6361 analogues to provide better energy scores than T6361, and have similar interactions with the binding site of E.coliMurA namely,3-{[2-(piperidine-1-carbonyl) phenyl]sulfamoyl}benzoic acid and 3-{[2-(pyrrolidine-1 carbonyl)phenyl]sulfamoyl}benzoic acid. Moreover, the two molecules were found to possess good pharmacokinetics and low toxicity.

Conclusion: We propose two analogues of T6361 as new potential inhibitors of MurA enzyme. Their good ADME-Toxicity profile qualifies them to reach in vitro and in vivo assays as future lead molecules.

Keywords: ADME-Toxicity profile.; Docking; FlexX; Key words: Antibacterial agents; MurA (UDP-N-Acetylglucosamine Enolpyruvyl Transferase).