Antimalarial activities of ferroquine conjugates with either glutathione reductase inhibitors or glutathione depletors via a hydrolyzable amide linker

作者：Chavain Natascha^*; Davioud Charvet Elisabeth; Trivelli Xavier; Mbeki Linda; Rottmann Matthias; Brun Reto; Biot Christophe

来源：Bioorganic & Medicinal Chemistry, 2009, 17(23): 8048-8059.

DOI：10.1016/j.bmc.2009.10.008

• Bioorganometallics
• Dual drugs
• Hemozoin
• Glutathione reductase
• Mechanism of action

Based on the prodrug concept as well as the combination of two different classes of antimalarial agents, we designed and synthesized two series of ferrocenic antimalarial dual molecules consisting of a ferroquine analogue conjugated with a glutathione reductase inhibitor (or a glutathione depletor) through a cleavable amide bond in order to target two essential pathways in the malarial parasites. The results showed no enhancement of the antimalarial activity of the dual molecules but evidenced a unique mode of action of ferroquine and ferrocenyl analogues distinct of those of chloroquine and nonferrocenic 4-aminoquinoline analogues.

• 出版日期2009-12-1
• 单位河北医科大学