Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines.

Description

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.

Links & Downloads

1. Sola I, Artigas A, Taylor MC et al (2014) Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines. Bioorganic & Medicinal Chemistry Letters, 24(23): 5435-5438.
2. http://hdl.handle.net/10454/7496
3. https://doi.org/10.1016/j.bmcl.2014.10.025

Tags

Molecular dimerization

Trypanocidal agents

Antimalarial agents

Bis(4-aminoquinolines)

Brain permeability

Additional Fields

Identifer	oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/7496
Date	27 October 2014
Creators	Sola, I., Artigas, A., Taylor, M.C., Gbedema, Stephen Y., Perez, B., Clos, M.V., Wright, Colin W., Kelly, J.M., Muñoz-Torrero, D.
Source Sets	Bradford Scholars
Language	English
Detected Language	English
Type	Article, Accepted manuscript
Rights	© 2014 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/, CC-BY-NC-ND