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

Irene Sola; Albert Artigas; Martin C. Taylor; Stephen Y. Gbedema; Belén Pérez; M. Victòria Clos; Colin W. Wright; John M. Kelly; Diego Muñoz-Torrero

doi:10.1016/j.bmcl.2014.10.025

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

Irene Sola, Albert Artigas, Martin C. Taylor, Stephen Y. Gbedema, Belén Pérez, M. Victòria Clos, Colin W. Wright, John M. Kelly, Diego Muñoz-Torrero

Research output: Contribution to journal › Article › Research › peer-review

11 Citations (Scopus)

Abstract

© 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.

Original language	English
Pages (from-to)	5435-5438
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2014.10.025
Publication status	Published - 1 Dec 2014

Keywords

Antimalarial agents
Bis(4-aminoquinolines)
Brain permeability
Molecular dimerization
Trypanocidal agents

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Sola, Irene ; Artigas, Albert ; Taylor, Martin C. ; Gbedema, Stephen Y. ; Pérez, Belén ; Clos, M. Victòria ; Wright, Colin W. ; Kelly, John M. ; Muñoz-Torrero, Diego. / Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines. In: Bioorganic and Medicinal Chemistry Letters. 2014 ; Vol. 24, No. 23. pp. 5435-5438.

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abstract = "{\textcopyright} 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.",

keywords = "Antimalarial agents, Bis(4-aminoquinolines), Brain permeability, Molecular dimerization, Trypanocidal agents",

author = "Irene Sola and Albert Artigas and Taylor, {Martin C.} and Gbedema, {Stephen Y.} and Bel{\'e}n P{\'e}rez and Clos, {M. Vict{\`o}ria} and Wright, {Colin W.} and Kelly, {John M.} and Diego Mu{\~n}oz-Torrero",

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Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines. / Sola, Irene; Artigas, Albert; Taylor, Martin C.; Gbedema, Stephen Y.; Pérez, Belén; Clos, M. Victòria; Wright, Colin W.; Kelly, John M.; Muñoz-Torrero, Diego.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 23, 01.12.2014, p. 5435-5438.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines

AU - Sola, Irene

AU - Artigas, Albert

AU - Taylor, Martin C.

AU - Gbedema, Stephen Y.

AU - Pérez, Belén

AU - Clos, M. Victòria

AU - Wright, Colin W.

AU - Kelly, John M.

AU - Muñoz-Torrero, Diego

PY - 2014/12/1

Y1 - 2014/12/1

N2 - © 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.

AB - © 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.

KW - Antimalarial agents

KW - Bis(4-aminoquinolines)

KW - Brain permeability

KW - Molecular dimerization

KW - Trypanocidal agents

U2 - 10.1016/j.bmcl.2014.10.025

DO - 10.1016/j.bmcl.2014.10.025

M3 - Article

VL - 24

SP - 5435

EP - 5438

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 23

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