Petrillo Francesco, Maione Angela, Spampinato Marisa, Massa Lea Di, Guida Marco, Zarrelli Armando, Galdiero Emilia, Longobardo Luigi
Department of Medical Sciences, Eye Clinic, Turin University, 10024 Turin, Italy.
Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy.
Antibiotics (Basel). 2025 Apr 25;14(5):432. doi: 10.3390/antibiotics14050432.
Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment options mainly rely on azoles and polyenes, which are known for their poor penetration into ocular tissue and associated toxicity. Moreover, conventional antifungals are usually ineffective when tested against biofilm-associated infections, mainly due to the metabolically inactive state of dormant cells embedded in the extracellular biofilm matrix. Here, analysis of the antifungal activity of four 2-aminobenzoic acid derivatives synthesized using a green method and their combination with Fluconazole (FLC) showed efficacy against the FLC-resistant clinical isolate of under both planktonic and biofilm formation conditions. Results showed that compounds and exhibited the best antifungal activity in the checkerboard association test, presenting a synergistic effect towards antifungal action. The downregulation of , , and genes during biofilm inhibition suggested a reduced capacity of the four compounds for hyphal growth and adhesion, as well as a decrease in pathogenicity due to the downregulation of some genes. and toxicity profiles indicated that these compounds exhibited low toxicity, as well as the absence of genotoxic effects. Therefore, green-synthetized 2-aminobenzoic acid derivatives may have potential as antifungal agents for the inhibition of growth and biofilm formation.
眼部真菌感染是一种进展缓慢的疾病,主要影响角膜,但也可能累及整个眼球。 是最常涉及的菌种之一。诊断和治疗这些感染都需要迅速而有效的行动。然而,目前可用的治疗选择主要依赖于唑类和多烯类药物,这些药物以其对眼部组织的渗透性差和相关毒性而闻名。此外,传统抗真菌药物在针对生物膜相关感染进行测试时通常无效,主要是因为嵌入细胞外生物膜基质中的休眠细胞处于代谢不活跃状态。在此,对使用绿色方法合成的四种2-氨基苯甲酸衍生物及其与氟康唑(FLC)的组合的抗真菌活性分析表明,在浮游和生物膜形成条件下,它们对耐FLC的临床分离株 均具有疗效。结果表明,化合物 和 在棋盘联合试验中表现出最佳的抗真菌活性,对抗真菌作用呈现协同效应。生物膜抑制过程中 、 和 基因的下调表明这四种化合物的菌丝生长和粘附能力降低,并且由于一些 基因的下调导致致病性降低。 和 的毒性谱表明这些化合物表现出低毒性,并且没有遗传毒性作用。因此,绿色合成的2-氨基苯甲酸衍生物可能具有作为抗真菌剂抑制 生长和生物膜形成的潜力。