Screening of small molecular inhibitors targeting at Toxoplasma gondii autophagy-related protein TgAtg8-TgAtg3 interaction
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- 英文论文题名：Screening of small molecular inhibitors targeting at Toxoplasma gondii autophagy-related protein TgAtg8-TgAtg3 interaction
- 论文作者：Shu Xian Liu ; Yue Hu ; Xin Hu ; Feng Tan
- 英文论文作者：Shu Xian Liu ; Yue Hu ; Xin Hu ; Feng Tan ; Department of Parasitology in Wenzhou Medical University ; Institute of Tropical Medicine in Wenzhou Medical University
- 年：2016
- 作者机构：Department of Parasitology in Wenzhou Medical University;Institute of Tropical Medicine in Wenzhou Medical University;
- 英文论文关键词：Toxoplasma gondii ; protein-protein interaction ; Atg8 ; Atg3 ; small-molecule inhibitor
- 会议召开时间：2016-08-08
- 会议录名称：中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会论文摘要集
- 英文会议录名称：The Abstracts of the Tenth Symposium for Yong Scientists of China Society of Parasitology
- 语种：英文
- 分类号：R382.5
- 学会代码：JISC
- 会议名称：中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会
- 会议地点：中国四川成都
- 主办单位：中国动物学会寄生虫学专业青年委员会
- 学会名称：中国动物学会寄生虫学专业委员会
- 页数：1
- 文件大小：339k
- 原文格式：D
- 会议级别：全国
摘要
Objective: To acquire small molecule inhibitors that could significantly reduce the proliferation of Toxoplasma gondii and have no(or low) toxicity to the human cells. Methods: Primarily, Alphascreen and SPR assays were used to detect the inhibitory activity of small molecule compounds on human LC-Atg3 、rat Atg8-Atg3 protein-protein interaction,respectively,selected compounds that had no effect on human Atg8-Atg3 interaction, thus obtained the small molecule compounds which could specifically impact on Toxoplasma gondii and have no influence in Atg8-Atg3 interaction of human cells. Meanwhile, we evaluated the specific inhibition effects of small molecule inhibitors at the level of cytology experiments: we used plaque assays and intracellular replication assays to choose the small molecule compounds that have no toxicity to host cells and further grope the concentration of the chosen inhibitors to identity their IC50. Then estimate the internal effect of Toxoplasma gondii infected mice model by drugs. Light spot experiments were applied to judge whether our drugs inhibit the interaction of TgAtg8-TgAtg3 or not by means of observing the formation of autophagosomes Atg8-PE complexes. Results: Experiments in vivo had already screened 12 small molecule inhibitors and a small molecule agonist, this 13 small molecule compounds are clinical medicines. Plaque assays indicated that 7 small molecular compounds in our lab have definitely inhibitory activity on the proliferation of Toxoplasma gondii and have no toxicity on host cells. Spot light experiments manifested that several drugs inhibit the interaction of TgAtg8-TgAtg3.Conclusion: It was illuminated preliminary that small molecule compounds reduce the proliferation of Toxoplasma gondii targeting at the interaction of TgAtg8-TgAtg3.
Objective: To acquire small molecule inhibitors that could significantly reduce the proliferation of Toxoplasma gondii and have no(or low) toxicity to the human cells. Methods: Primarily, Alphascreen and SPR assays were used to detect the inhibitory activity of small molecule compounds on human LC-Atg3 、rat Atg8-Atg3 protein-protein interaction,respectively,selected compounds that had no effect on human Atg8-Atg3 interaction, thus obtained the small molecule compounds which could specifically impact on Toxoplasma gondii and have no influence in Atg8-Atg3 interaction of human cells. Meanwhile, we evaluated the specific inhibition effects of small molecule inhibitors at the level of cytology experiments: we used plaque assays and intracellular replication assays to choose the small molecule compounds that have no toxicity to host cells and further grope the concentration of the chosen inhibitors to identity their IC50. Then estimate the internal effect of Toxoplasma gondii infected mice model by drugs. Light spot experiments were applied to judge whether our drugs inhibit the interaction of TgAtg8-TgAtg3 or not by means of observing the formation of autophagosomes Atg8-PE complexes. Results: Experiments in vivo had already screened 12 small molecule inhibitors and a small molecule agonist, this 13 small molecule compounds are clinical medicines. Plaque assays indicated that 7 small molecular compounds in our lab have definitely inhibitory activity on the proliferation of Toxoplasma gondii and have no toxicity on host cells. Spot light experiments manifested that several drugs inhibit the interaction of TgAtg8-TgAtg3.Conclusion: It was illuminated preliminary that small molecule compounds reduce the proliferation of Toxoplasma gondii targeting at the interaction of TgAtg8-TgAtg3.
Objective: To acquire small molecule inhibitors that could significantly reduce the proliferation of Toxoplasma gondii and have no(or low) toxicity to the human cells. Methods: Primarily, Alphascreen and SPR assays were used to detect the inhibitory activity of small molecule compounds on human LC-Atg3 、rat Atg8-Atg3 protein-protein interaction,respectively,selected compounds that had no effect on human Atg8-Atg3 interaction, thus obtained the small molecule compounds which could specifically impact on Toxoplasma gondii and have no influence in Atg8-Atg3 interaction of human cells. Meanwhile, we evaluated the specific inhibition effects of small molecule inhibitors at the level of cytology experiments: we used plaque assays and intracellular replication assays to choose the small molecule compounds that have no toxicity to host cells and further grope the concentration of the chosen inhibitors to identity their IC50. Then estimate the internal effect of Toxoplasma gondii infected mice model by drugs. Light spot experiments were applied to judge whether our drugs inhibit the interaction of TgAtg8-TgAtg3 or not by means of observing the formation of autophagosomes Atg8-PE complexes. Results: Experiments in vivo had already screened 12 small molecule inhibitors and a small molecule agonist, this 13 small molecule compounds are clinical medicines. Plaque assays indicated that 7 small molecular compounds in our lab have definitely inhibitory activity on the proliferation of Toxoplasma gondii and have no toxicity on host cells. Spot light experiments manifested that several drugs inhibit the interaction of TgAtg8-TgAtg3.Conclusion: It was illuminated preliminary that small molecule compounds reduce the proliferation of Toxoplasma gondii targeting at the interaction of TgAtg8-TgAtg3.
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