抗疟天然产物溴叶藻素A的药代动力学、代谢及疗效
Pharmacokinetics, metabolism, and efficacy of the antimalarial natural product bromophycolide A.
作者信息
Teasdale Margaret E, Prudhomme Jacques, Torres Manuel, Braley Matthew, Cervantes Serena, Bhatia Shanti C, La Clair James J, Le Roch Karine, Kubanek Julia
机构信息
School of Biology and School of Chemistry and Biochemistry, Aquatic Chemical Ecology Center and Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
出版信息
ACS Med Chem Lett. 2013 Oct 10;4(10):989-993. doi: 10.1021/ml4002858.
Abstract
A suite of pharmacokinetic and pharmacological studies show that bromophycolide A (), an inhibitor of drug-sensitive and drug-resistant , displays a typical small molecule profile with low toxicity and good bioavailability. Despite susceptibility to liver metabolism and a short half-life, significantly decreased parasitemia in a malaria mouse model. Combining these data with prior SAR analyses, we demonstrate the potential for future development of and its bioactive ester analogs.
摘要
一系列药代动力学和药理学研究表明，对药物敏感和耐药的疟原虫具有抑制作用的溴代藻内酯A（）显示出典型的小分子特征，具有低毒性和良好的生物利用度。尽管它易受肝脏代谢影响且半衰期较短，但在疟疾小鼠模型中可显著降低疟原虫血症。将这些数据与之前的构效关系分析相结合，我们证明了其及其生物活性酯类似物未来开发的潜力。
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