Investigating the activity of quinine analogues versus chloroquine resistant Plasmodium falciparum

详细信息	查看全文 | 推荐本文 |

• 作者：Theresa Dinio^a ; Alexander P. Gorka^b ; ^c ; Andrew McGinniss^a ; Paul D. Roepe^b ; ^c ; Jeremy B. Morgan^a ; ^{morganj@uncw.edu}
• 关键词：Malaria ; Plasmodium ; Cinchona ; Quinine ; Heck reaction
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 May, 2012
• 卷：20
• 期：10
• 页码：3292-3297
• 文件大小：548 K

摘要

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 IC₅₀ values relative to QN.