Carter Melissa D, Phelan Vanessa V, Sandlin Rebecca D, Bachmann Brian O, Wright David W
Vanderbilt University, Department of Chemistry, Station B 351822, Nashville, TN 37235, USA.
Comb Chem High Throughput Screen. 2010 Mar;13(3):285-92. doi: 10.2174/138620710790980496.
The growing drug resistance of Plasmodia spp. to current antimalarial agents in the quinine and artemisinin families further asserts the need for novel drug classes to combat malaria infection. One approach to the discovery of new antimalarials is the screening of natural product extracts for activity against the formation of hemozoin, a biomineral essential to parasite survival. By mimicking the in vivo lipid-water interface at which native hemozoin is found, hemozoin can be synthesized outside the parasite. In this work, a variety of lipophilic mediators was used to determine the optimal platform for in vitro hemozoin formation and then tested for efficacy in preliminary screens containing crude natural product extracts. The complete optimization and validation of a NP-40 detergent-mediated assay provide a screening template with an expedited 4-hour incubation time and identical IC50 values to those measured from the parasite's native lipid component.
疟原虫属对奎宁和青蒿素家族中当前抗疟药物的耐药性不断增强，这进一步凸显了需要新型药物类别来对抗疟疾感染。发现新抗疟药的一种方法是筛选天然产物提取物，以检测其对疟原虫生存所必需的生物矿物质——疟原虫色素形成的活性。通过模拟发现天然疟原虫色素的体内脂质 - 水界面，可以在寄生虫体外合成疟原虫色素。在这项工作中，使用了多种亲脂性介质来确定体外疟原虫色素形成的最佳平台，然后在含有天然产物粗提物的初步筛选中测试其功效。NP - 40去污剂介导的测定法的完全优化和验证提供了一个筛选模板，其孵育时间缩短至4小时，且IC50值与从寄生虫天然脂质成分测得的值相同。
