Quinoline–Pyrimidine Hybrids: Synthesis, Antiplasmodial Activity, SAR, and Mode of Action Studies

详细信息    查看全文

• 作者：Kamaljit Singh ; Hardeep Kaur ; Peter Smith ; Carmen de Kock ; Kelly Chibale ; Jan Balzarini
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：January 23, 2014
• 年：2014
• 卷：57
• 期：2
• 页码：435-448
• 全文大小：670K
• ISSN：1520-4804

文摘

For the treatment of malaria which affects nearly 200 million people each year and the continued exacerbation by the emergence of drug resistance to most of the available antimalarials, the 鈥渃ovalent bitherapy鈥?suggests hybrid molecules to be the next-generation antimalarial drugs. In this investigation, new hybrids of 4-aminoquinoline and pyrimidine moieties that show antiplasmodial activity in the nM range against chloroquine-resistant as well as chloroquine-sensitive strains of Plasmodium falciparum have been prepared. Cytotoxicity evaluation and mode of action of most potent hybrid molecule have been conducted.