Jimenez Diana Liz, da Silva Débora Taisa Keller, da Paz Costa Sauda Talita, de Almeida-Apolonio Adriana Araújo, Roque Emanuele P O, de Castilho Pamella Fukuda, de Andrade Dos Santos João Víctor, Silva Sidnei M, Pizzuti Lucas, Junior Amilcar M, Deflon Victor M, de Oliveira Kelly Mari Pires, Casagrande Gleison Antônio
Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, 79804-970 Dourados, MS, Brazil.
Grupo de Pesquisa em Síntese e Caracterização Molecular, Universidade Federal de Mato Grosso do Sul - Instituto de Química, 79074-460 Campo Grande, MS, Brazil.
J Inorg Biochem. 2025 Oct;271:112980. doi: 10.1016/j.jinorgbio.2025.112980. Epub 2025 Jun 26.
Overgrowth of Candida spp., known for its strong adhesion to biotic and abiotic surfaces, makes treatment difficult in denture stomatitis. To address this challenge, two novel cadmium(II) complexes containing 2,5-pyridinedicarboxylic acid (HL) (complex 1 [Cd(HL)(HO)(DMSO)I] and [Cd(HL)(HO)(bipy)I] complex 2), were synthesized and fully characterized by X-ray diffractometry, HRMS-ESI (+) spectrometry, H and C NMR, FT-IR and elemental analysis. These complexes were evaluated for their antifungal, antibiofilm, hemolytic, and mutagenic properties. The interaction of these complexes with established antifungal agents was also investigated. Both complexes demonstrated remarkable antifungal activity, particularly against C. albicans and C. krusei, with MIC ranging from 62.5 (97.91 μM) to 0.48 (0.75 μM) μg/mL and MFC from 125 (195.82 μM) to 3.80 (5.95 μM) μg/mL. Furthermore, these complexes effectively inhibited C. krusei biofilm formation on prosthetic acrylic resin test specimens, with complex 2 showing superior activity. The complexes also displayed synergistic effects with fluconazole, furthermore, sorbitol assays have shown that cell wall is one of the targets of the tested complexes. Importantly, hemolysis assays indicated that the complexes were non-cytotoxic to human erythrocytes, and mutagenicity assays confirmed their non-mutagenic nature. These findings suggest that the synthesized cadmium(II) complexes, particularly complex 2, possess significant potential as therapeutic agents for the treatment of denture stomatitis and oral candidiasis in general.
念珠菌属过度生长以其对生物和非生物表面的强粘附性而闻名,这使得义齿性口炎的治疗变得困难。为应对这一挑战,合成了两种含2,5-吡啶二甲酸(HL)的新型镉(II)配合物(配合物1 [Cd(HL)(HO)(DMSO)I] 和配合物2 [Cd(HL)(HO)(bipy)I]),并通过X射线衍射法、高分辨质谱-电喷雾电离(+)光谱法、氢和碳核磁共振、傅里叶变换红外光谱和元素分析对其进行了全面表征。对这些配合物的抗真菌、抗生物膜、溶血和致突变特性进行了评估。还研究了这些配合物与既定抗真菌剂的相互作用。两种配合物均表现出显著的抗真菌活性,尤其是对白色念珠菌和克鲁斯念珠菌,其最低抑菌浓度(MIC)范围为62.5(97.91 μM)至0.48(0.75 μM)μg/mL,最低杀菌浓度(MFC)范围为125(195.82 μM)至3.80(5.95 μM)μg/mL。此外,这些配合物有效地抑制了克鲁斯念珠菌在义齿丙烯酸树脂测试标本上的生物膜形成,配合物2表现出更强的活性。这些配合物与氟康唑还显示出协同作用,此外,山梨醇测定表明细胞壁是所测试配合物的作用靶点之一。重要的是,溶血试验表明这些配合物对人红细胞无细胞毒性,致突变试验证实了它们的非致突变性。这些发现表明,合成的镉(II)配合物,特别是配合物2,作为治疗义齿性口炎和一般口腔念珠菌病的治疗剂具有巨大潜力。