© 2014 Elsevier Ltd. All rights reserved. We have synthesized a series of dimers of (+)-(7R,11R)-huprine Y and evaluated their activity against Trypanosoma brucei, Plasmodium falciparum, rat myoblast L6 cells and human acetylcholinesterase (hAChE), and their brain permeability. Most dimers have more potent and selective trypanocidal activity than huprine Y and are brain permeable, but they are devoid of antimalarial activity and remain active against hAChE. Lead optimization will focus on identifying compounds with a more favourable trypanocidal/anticholinesterase activity ratio.
- Antimalarial agents
- Brain permeability
- Molecular dimerization
- Trypanocidal agents
Sola, I., Artigas, A., Taylor, M. C., Gbedema, S. Y., Pérez, B., Clos, M. V., Wright, C. W., Kelly, J. M., & Muñoz-Torrero, D. (2014). Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines. Bioorganic and Medicinal Chemistry Letters, 24(23), 5435-5438. https://doi.org/10.1016/j.bmcl.2014.10.025