Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
Antimalarial activities of ferroquine conjugates with either glutathione reductase inhibitors or glutathione depletors via a hydrolyzable amide linker
Journal
Bioorganic & medicinal chemistry : a Tetrahedron publication for the rapid dissemenination of full original research papers and critical reviews on biomolecular chemistry, medicinal chemistry and related disciplines
Volume
17
Number
23
Pages / Article-Number
8048-8059
Keywords
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.
