Department of Chemistry and Biochemistry, University of North Carolina, Wilmington, Dobo Hall, 601 S. College Road, Wilmington, NC 28403, USA.
Bioorg Med Chem. 2012 May 15;20(10):3292-7. doi: 10.1016/j.bmc.2012.03.042. Epub 2012 Mar 29.
Plasmodium falciparum, the deadliest malarial parasite species, has developed resistance against nearly all man-made antimalarial drugs within the past century. However, quinine (QN), the first antimalarial drug, remains efficacious worldwide. Some chloroquine resistant (CQR) P. falciparum strains or isolates show mild cross resistance to QN, but many do not. Further optimization of QN may provide a well-tolerated therapy with improved activity versus CQR malaria. Thus, using the Heck reaction, we have pursued a structure-activity relationship study, including vinyl group modifications of QN. Certain derivatives show good antiplasmodial activity in QN-resistant and QN-sensitive strains, with lower IC(50) values relative to QN.
恶性疟原虫（Plasmodium falciparum）是最致命的疟原虫物种，在过去一个世纪中已经对几乎所有人工合成的抗疟药物产生了耐药性。然而，奎宁（QN）作为第一种抗疟药物，在全球范围内仍然有效。一些对氯喹有抗性（CQR）的恶性疟原虫株或分离株对 QN 表现出轻微的交叉抗性，但许多则没有。进一步优化 QN 可能提供一种耐受性良好的治疗方法，对 CQR 疟疾具有更好的活性。因此，我们使用 Heck 反应进行了构效关系研究，包括 QN 的乙烯基修饰。某些衍生物在 QN 耐药和 QN 敏感株中表现出良好的抗疟原虫活性，与 QN 相比，IC（50）值更低。
