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Current Topics in Medicinal Chemistry

Author(s): Dora C.S. Costa, Thamires Q. Froes, Marina S. Mendes, Luana da S.M. Forezi, Vitor F. Ferreira, Marcelo S. Castilho* and Fernando de C. da Silva*

DOI: 10.2174/0115680266327024240726111230

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1H-1,2,3-triazol-1,4-naphthoquinone Derivatives: Novel Inhibitors Targeting Pyocyanin Biosynthesis for P. Aeruginosa Infection Treatment Advances

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Abstract

Background: This study investigates the potential of eleven 1H-1,2,3-triazol-1,4-naphthoquinone conjugates as virulence factor inhibitors (like Pyocyanin) and their affinity for PhzM, a crucial enzyme for Pyocyanin biosynthesis in Pseudomonas aeruginosa infections.

Methods: A straightforward synthetic pathway enabled the production of these compounds, which were characterized and structurally confirmed through spectroscopic analyses. Evaluation of their impact on PhzM thermal stability identified promising candidates for PhzM binders.

Results: Concentration-response behavior elucidated their binding affinity, revealing them as the first reported micromolar affinity ligands for PhzM. Structure-activity relationship analysis emphasized the role of specific molecular moieties in binding affinity modulation, paving the way for future advanced inhibitors’ development.

Conclusion: These findings highlight the potential of naphthoquinone-triazole derivatives as leads for novel therapeutics against P. aeruginosa infections.

Keywords: 1H-1, 2, 3-Triazol-1, 4-naphthoquinone, Novel inhibitors, Pyocyanin, P. aeruginosa, Spectroscopic analyses, PhzM binders.

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