Departamento de Química Orgânica, Universidade Federal Fluminense, Instituto de Química, Niterói, RJ, 24020, 150, Brazil.
Programa de pós-graduação em Biotecnologia da Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil.
Curr Top Med Chem. 2024;24(24):2161-2171. doi: 10.2174/0115680266327024240726111230.
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 infections.
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.
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.
These findings highlight the potential of naphthoquinone-triazole derivatives as leads for novel therapeutics against infections.
本研究调查了 11 个 1H-1,2,3-三唑-1,4-萘醌化合物作为毒力因子抑制剂（如绿脓菌素）的潜力，以及它们对 PhzM 的亲和力，PhzM 是 感染中绿脓菌素生物合成的关键酶。
通过直接的合成途径生产了这些化合物，通过光谱分析对其进行了表征和结构确证。评估它们对 PhzM 热稳定性的影响，确定了 PhzM 结合物的有前途的候选物。
浓度反应行为阐明了它们的结合亲和力，表明它们是第一个报道的对 PhzM 具有微摩尔亲和力的配体。构效关系分析强调了特定分子片段在结合亲和力调节中的作用，为未来开发更先进的抑制剂铺平了道路。
这些发现强调了萘醌-三唑衍生物作为治疗 感染的新型治疗药物的潜在先导化合物。
