Antiadhesive glycoconjugate metal complexes targeting pathogens Pseudomonas aeruginosa and Candida albicans.

IF 2.7 3区化学 Q1 CHEMISTRY, ORGANIC

Organic & Biomolecular Chemistry Pub Date : 2025-07-02 DOI:10.1039/d5ob00970g

Karolina Wojtczak, Emilie Gillon, Diana Bura, Karen Richmond, Megan Joyce, Emma Caraher, Keela Kessie, Trinidad Velasco-Torrijos, Cristina Trujillo, Anne Imberty, Kevin Kavanagh, Gordon Cooke, Joseph P Byrne

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Abstract

Glycoconjugates are known to interact with carbohydrate-binding proteins involved in adhesion by pathogens, and offer opportunities to design antimicrobial agents. Metal complexes with Eu(III), Ni(II) and Zn(II) were prepared from glycoconjugate ligand 1Gal, which binds to P. aeruginosa's lectin LecA (K_d 9.6 ± 0.7 μM). In vitro anti-adhesive activity of these compounds was evaluated for both P. aeruginosa and C. albicans. Choice of metal ion played a crucial role in modulating anti-adhesive activity, with Eu(III) complexes most effective: [Eu·(1Gal)(H₂O)₆](CF₃SO₃)₃ inhibits 60% biofilm formation by P. aeruginosa and [Eu·(1Gal)₃](CF₃SO₃)₃ inhibits 62% of C. albicans adhesion to buccal epithelial cells (both at 0.1 mM). The results presented demonstrate the potential for metal coordination to significantly enhance biological activity of glycoconjugates, surpassing the effect of the ligand's modest lectin-binding affinity alone.

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针对病原菌铜绿假单胞菌和白色念珠菌的抗粘附糖结合金属配合物。

已知糖缀合物与参与病原体粘附的碳水化合物结合蛋白相互作用，并为设计抗菌剂提供了机会。利用糖缀合配体1Gal制备了Eu（III）、Ni（II）和Zn（II）金属配合物，与铜绿假单胞菌的凝集素LecA （Kd 9.6±0.7 μM）结合。研究了这些化合物对铜绿假单胞菌和白色假单胞菌的体外抗粘附活性。金属离子的选择在调节抗粘附活性中起着至关重要的作用，其中Eu（III）配合物最有效：[Eu·（1Gal）（H2O）6](CF3SO3)3抑制铜绿假单胞菌60%的生物膜形成，[Eu·（1Gal）3](CF3SO3)3抑制62%的白色念珠菌对口腔上皮细胞的粘附（均为0.1 mM）。研究结果表明，金属配位可以显著提高糖缀合物的生物活性，超过配体仅具有适度的凝集素结合亲和力的作用。

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来源期刊

Organic & Biomolecular Chemistry 化学-有机化学

CiteScore

5.50

自引率

9.40%

发文量

1056

审稿时长

1.3 months

期刊介绍： Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.