Department of Chemistry, Tuskegee University, Tuskegee, AL, USA.
Department of Biology, Tuskegee University, Tuskegee, AL, USA.
Chem Biol Drug Des. 2018 Jan;91(1):194-201. doi: 10.1111/cbdd.13070. Epub 2017 Aug 11.
Toxoplasmosis is one of the most neglected zoonotic foodborne parasitic diseases that cause public health and socioeconomic concern worldwide. The current drugs used for the treatment of toxoplasmosis have been identified to have clinical limitations. Hence, new drugs are urgently needed to eradicate T.gondii infections globally. Here, an in vitro anti-Toxoplasma gondii activity of taxifolin (dihydroquercetin) and dihydrofolate inhibitor (pyrimethamine) alone and in combination with a fixed concentration of pyrimethamine were investigated against the rapidly proliferating T.gondii RH strain at 48 hr using colorimetric assay. Pyrimethamine showed the highest anti-T. gondii activity with IC of 0.84 μg/ml (p > .05), respectively. The combination of pyrimethamine with dihydroquercetin gave a significant inhibitory activity against tachyzoites in in vitro with IC of 1.39 μg/ml (p < .05). The IC ranges obtained for the individual and the combination of taxifolin with pyrimethamine inhibition of parasite growth were not cytotoxic to the infected HFF and Hek-293 cell lines used. These compounds combination should be investigated further using in vivo model of toxoplasmosis.
弓形虫病是一种最容易被忽视的动物源性食源性寄生虫病,在全球范围内引起公共卫生和社会经济方面的关注。目前用于治疗弓形虫病的药物已被确定具有临床局限性。因此,迫切需要新的药物来在全球范围内消除弓形体感染。在这里,使用比色法在 48 小时内单独和联合固定浓度的嘧啶胺研究了二氢槲皮素(二氢槲皮素)和二氢叶酸抑制剂(乙胺嘧啶)对快速增殖的 T.gondii RH 株的体外抗弓形虫活性。嘧啶胺对 T. gondii 的抗活性最高,IC 为 0.84 μg/ml(p>.05)。嘧啶胺与二氢槲皮素联合使用对体外速殖子具有显著的抑制活性,IC 为 1.39 μg/ml(p<.05)。单独使用和联合使用二氢槲皮素抑制寄生虫生长的 IC 范围对所用感染的 HFF 和 Hek-293 细胞系没有细胞毒性。应进一步使用弓形虫病的体内模型来研究这些化合物的组合。