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

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© 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.

Idioma original	Anglès
Pàgines (de-a)	5435-5438
Revista	Bioorganic and Medicinal Chemistry Letters
Volum	24
Número	23
DOIs	https://doi.org/10.1016/j.bmcl.2014.10.025
Estat de la publicació	Publicada - 1 de des. 2014

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10.1016/j.bmcl.2014.10.025

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

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",

year = "2014",

month = dec,

day = "1",

doi = "10.1016/j.bmcl.2014.10.025",

language = "English",

volume = "24",

pages = "5435--5438",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "23",

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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

UR - https://www.scopus.com/pages/publications/84910146091

U2 - 10.1016/j.bmcl.2014.10.025

DO - 10.1016/j.bmcl.2014.10.025

M3 - Article

SN - 0960-894X

VL - 24

SP - 5435

EP - 5438

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

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

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