Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, 36104, USA.
Microbiology PhD Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, 36104, USA.
Parasit Vectors. 2023 Aug 3;16(1):261. doi: 10.1186/s13071-023-05849-3.
Quercetin (QUE) is a natural polyphenol known to have numerous pharmacological properties against infectious and non-infectious diseases. Azithromycin (AZ) is an antibiotic that belongs to the azalide class of antimicrobials and an antiparasitic that is known to be effective in combination with clindamycin against pyrimethamine/sulfadiazine-resistant Toxoplasma gondii tachyzoites in clinical settings. Both compounds are known to target protein synthesis and have anti-inflammatory properties. However, little is known about QUE and AZ synergistic interaction against T. gondii growth. Here, we report for the first time the effects of the combination of QUE and AZ on T. gondii growth. The 50% inhibitory concentration (IC) for QUE at 72 h of interaction was determined to be 0.50 µM, whereas AZ gave an IC value of 0.66 µM at 72 h of interaction with parasites. Combination testing of QUE and AZ in a ratio of 2:1 (QUE:AZ) showed an IC value of 0.081 µM. Interestingly, a fractional inhibitory index value of 0.28 was observed, indicating a strong synergy. QUE was also found to upregulate the generation of reactive oxygen species and cause dysfunction of the mitochondria membrane of both intracellular and extracellular T. gondii tachyzoites. Overall, the results indicate that QUE is a novel lead capable of synergizing with AZ for inhibiting T. gondii growth and may merit future investigation in vivo for possible combination drug development.
槲皮素（QUE）是一种天然多酚，具有多种针对感染性和非感染性疾病的药理学特性。阿奇霉素（AZ）是一种抗生素，属于氮杂内酯类抗生素和抗寄生虫药，已知与克林霉素联合使用对临床环境中嘧啶甲胺/磺胺嘧啶耐药的刚地弓形虫速殖子有效。这两种化合物都已知靶向蛋白质合成并具有抗炎特性。然而，关于 QUE 和 AZ 联合对抗弓形虫生长的协同作用知之甚少。在这里，我们首次报道了 QUE 和 AZ 联合对弓形虫生长的影响。在 72 小时的相互作用中，QUE 的 50%抑制浓度（IC）为 0.50µM，而 AZ 在与寄生虫相互作用 72 小时时的 IC 值为 0.66µM。QUE 和 AZ 以 2:1 的比例（QUE:AZ）进行组合测试，IC 值为 0.081µM。有趣的是，观察到 0.28 的分数抑制指数值，表明存在强烈的协同作用。QUE 还被发现上调活性氧的产生并导致细胞内和细胞外弓形虫速殖子的线粒体膜功能障碍。总体而言，这些结果表明 QUE 是一种有潜力的新型先导化合物，能够与 AZ 协同抑制弓形虫生长，可能值得进一步在体内进行研究，以开发可能的联合药物。
