Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, Three Gorges University, Yichang, 443002, China; Shanghai Institute of Infectious Diseases and Biosecurity & Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.
Shanghai Institute of Infectious Diseases and Biosecurity & Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.
Microb Pathog. 2024 Oct;195:106877. doi: 10.1016/j.micpath.2024.106877. Epub 2024 Aug 20.
Candida albicans is an opportunistic pathogen commonly found in human mucous membranes. In light of the escalating challenge posed by antibiotic resistance of C. albicans strains worldwide, it is an urgently necessary to explore alternative therapeutic options.
This study aims to assess the efficacy of two Cinnamaldehyde derivatives, 2-Cl Cinnamaldehyde (2-Cl CA) and 4-Cl Cinnamaldehyde (4-Cl CA), against C. albicans through both in vitro experiments and in vivo murine models and to evaluate their potential as new drug candidates for treating C. albicans.
The minimum inhibitory concentrations (MICs) of Cinnamaldehyde 2-Cl and 4-Cl benzene ring derivatives against C. albicans were 25 μg/mL. Time-killing experiments revealed that both Cinnamaldehyde derivatives exhibited fungicidal activity against C. albicans at concentrations of 5 MIC and 10 MIC. In the checkerboard experiment, 4-Cl CA did not show any antagonistic effect when combined with first-line antifungal drugs. Instead, it exhibited additive effects in combination with nystatin. Both 2-Cl and 4-Cl CA demonstrated inhibitory activity against C. albicans biofilm formation, especially at 8 MIC and 16 MIC concentrations. In C. albicans biofilm eradication experiments, although high drug concentrations of 2-Cl and 4-Cl CA were unable to eradicate the biofilm completely, they were still effective in killing C. albicans cells within the biofilm. Moreover, sub-inhibitory concentrations of 4-Cl CA (ranging from 5 to 20 μg/mL) significantly inhibited cell aggregation and hyphal formation. Furthermore, 4-Cl CA effectively inhibited intracellular C. albicans infection in macrophages. Lastly, the effectiveness of 4-Cl CA was evaluated in a mouse model of hematogenous disseminated candidiasis caused by C. albicans, which revealed that 4-Cl CA significantly reduced fungal burden and improved mouse survival compared to the untreated controls.
The 4-Cl CA exhibited inhibitory effects against C. albicans through both in vivo and in vitro models, demonstrating its therapeutic potential as a promising new drug candidate for treating drug-resistant candidiasis albicans.
白色念珠菌是一种常见的机会性病原体，存在于人体黏膜中。鉴于世界各地白色念珠菌菌株对抗生素耐药性的挑战日益加剧，探索替代治疗方案是当务之急。
本研究旨在通过体外实验和体内小鼠模型评估两种肉桂醛衍生物，2-Cl 肉桂醛（2-Cl CA）和 4-Cl 肉桂醛（4-Cl CA）对白色念珠菌的疗效，并评估它们作为治疗白色念珠菌的新型候选药物的潜力。
肉桂醛 2-Cl 和 4-Cl 苯环衍生物对白色念珠菌的最低抑菌浓度（MIC）分别为 25 μg/mL。时间杀伤实验表明，两种肉桂醛衍生物在浓度为 5 MIC 和 10 MIC 时对白色念珠菌均表现出杀菌活性。棋盘实验显示，4-Cl CA 与一线抗真菌药物联合使用时没有表现出拮抗作用，而与制霉菌素联合使用时表现出相加作用。2-Cl 和 4-Cl CA 均能抑制白色念珠菌生物膜的形成，特别是在 8 MIC 和 16 MIC 浓度下。在白色念珠菌生物膜清除实验中，虽然高浓度的 2-Cl 和 4-Cl CA 不能完全清除生物膜，但仍能有效杀死生物膜内的白色念珠菌细胞。此外，亚抑菌浓度的 4-Cl CA（5-20 μg/mL）显著抑制细胞聚集和菌丝形成。此外，4-Cl CA 能有效抑制巨噬细胞内白色念珠菌的感染。最后，在白色念珠菌引起的血源性播散性念珠菌病小鼠模型中评估了 4-Cl CA 的疗效，结果显示，与未治疗对照组相比，4-Cl CA 显著降低了真菌负荷并提高了小鼠生存率。
4-Cl CA 通过体内和体外模型对白色念珠菌均有抑制作用，表明其作为治疗耐药性白色念珠菌感染的有前途的新型候选药物具有治疗潜力。
