对微生物代谢物库的查和命中评价,以对抗致病性寄生虫Plasmodium falciparum和Toxoplasma gondii
Maria R Gancheva1, Emma Y Mao2, Ornella Romeo3
1Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, 5005, South Australia, Australia; ARC Training Centre for Environmental and Agricultural Solutions to Antimicrobial Resistance (CEAStAR), St Lucia, 4072, Queensland, Australia; School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, 5371, South Australia, Australia.
概括
自然产品为抗药性疟疾和毒素菌提供了新的希望. 查发现了强效的化合物,其中醇和多素显示出开发新型抗寄生虫药物的前景.
科学领域:
- 微生物学和自然产品化学
- 寄生虫学和药物发现
- 医学化学
背景情况:
- 对抗疟疾药物的新兴耐药性和对毒素的不理想治疗需要新的药物开发.
- 自然产品的结构多样性是发现新型抗寄生素化合物的宝贵来源.
- 像Plasmodium falciparum和Toxoplasma gondii这样的虫寄生虫对全球健康构成重大挑战.
研究的目的:
- 为了选BioAustralis发现板系列I图书馆针对Plasmodium falciparum和Toxoplasma gondii.
- 确定具有抗寄生虫活性和低哺乳动物细胞毒性的新型天然产品.
- 为开发新的抗寄生虫疗法提供起点.
主要方法:
- 对812种微生物天然产品进行查,以检测它们是否有Plasmodium falciparum和Toxoplasma gondii.
- 根据2μg/ml的增长抑制来确定活性化合物.
- 低哺乳动物细胞毒性选和体外半最大抑制度 (IC50) 的确定.
主要成果:
- 219种化合物抑制了P. falciparum的生长,149种化合物抑制了T. gondii的生长.
- 在活性剂中发现了50多种不同的化学化合物.
- 四组化合物显示出低纳米抗寄生素活性,而 thiazole 和 pleuromutilins 显示出有利的安全性.
结论:
- 生物澳大利亚发现板 I 系列含有针对重大虫寄生虫的活性化合物.
- 单环 thiazole 和 pleuromutilins 是进一步开发抗寄生虫药物的有希望的候选药物.
- 这项研究为寄生虫生物学研究和新型抗寄生虫药物发现提供了宝贵的工具.
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