Abugri Daniel A, Witola William H, Jaynes Jesse M
Department of Chemistry, College of Arts and Sciences, Laboratory of Ethnomedicine, Parasitology and Drug Discovery, Tuskegee University, Tuskegee, USA.
Department of Biology, College of Arts and Sciences, Tuskegee University, Tuskegee, AL, USA.
Parasitol Res. 2017 Dec;116(12):3387-3400. doi: 10.1007/s00436-017-5661-1. Epub 2017 Oct 30.
Toxoplasma gondii is a ubiquitous intracellular zoonotic parasite estimated to affect about 30-90% of the world's human population. The most affected are immunocompromised individuals such as HIV-AIDS and cancer patients, organ and tissue transplant recipients, and congenitally infected children. No effective and safe drugs and vaccines are available against all forms of the parasite. We report here the antagonistic and indifferent activity of the combination of five different formulations of pure synthetic 3-deoxyanthocyaninidin (3-DA) chloride compounds against T. gondii tachyzoites and the synergistic and additive interaction against a human foreskin fibroblast (HFF) cell line in vitro using fluorescence microscopy, trypan blue assay, and fractional inhibitory concentration index. The individual and the combined pure 3-DA compounds were observed to have effective inhibition against T. gondii parasites with less cytotoxic effect in a ratio of 1:1. The IC values for parasite inhibition ranged from 1.88 μg/mL (1.51-2.32 μg/mL) for luteolinindin plus 7-methoxyapigeninindin (LU/7-MAP) and 2.23 μg/mL (1.66-2.97 μg/mL) for apigeninindin plus 7-methoxyapigeninindin (AP/7-MAP) combinations at 95% confidence interval (CI) after 48 h of culture. We found LU/7-MAP to be antagonistic and AP/7-MAP to be indifferent in interaction against T. gondii growth. Both individual and combination 3-DA compounds not only depicted very strong inhibitory activity against T. gondii, but also had synergistic and additive cytotoxic effects against HFF cells. These synthetic 3-DAs have potential as antiparasitic agents for the treatment of human toxoplasmosis.
刚地弓形虫是一种广泛存在的细胞内人畜共患寄生虫，据估计全球约30%-90%的人口受其影响。受影响最严重的是免疫功能低下的个体，如艾滋病毒-艾滋病患者和癌症患者、器官和组织移植受者以及先天性感染儿童。目前尚无针对该寄生虫所有形式的有效且安全的药物和疫苗。我们在此报告了五种不同配方的纯合成氯化3-脱氧花青素（3-DA）化合物组合对刚地弓形虫速殖子的拮抗和无相互作用活性，以及使用荧光显微镜、台盼蓝试验和分数抑制浓度指数在体外对人包皮成纤维细胞（HFF）细胞系的协同和相加相互作用。观察到单独和组合的纯3-DA化合物对刚地弓形虫寄生虫具有有效的抑制作用，且细胞毒性较小，比例为1:1。培养48小时后，在95%置信区间（CI）下，木犀草素靛苷加7-甲氧基芹菜素靛苷（LU/7-MAP）组合对寄生虫抑制的IC值范围为1.88μg/mL（1.51-2.32μg/mL），芹菜素靛苷加7-甲氧基芹菜素靛苷（AP/7-MAP）组合为2.23μg/mL（1.66-2.97μg/mL）。我们发现LU/7-MAP对刚地弓形虫生长的相互作用具有拮抗作用，AP/7-MAP无相互作用。单独和组合的3-DA化合物不仅对刚地弓形虫具有很强的抑制活性，而且对HFF细胞具有协同和相加的细胞毒性作用。这些合成的3-DA有潜力作为抗寄生虫药物用于治疗人类弓形虫病。
