Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines

Pascal Marchand; Marc Antoine Bazin; Fabrice Pagniez; Guillaume Rivière; Lizeth Bodero; Sophie Marhadour; Marie Renée Nourrisson; Carine Picot; Sandrine Ruchaud; Stéphane Bach; Blandine Baratte; Michel Sauvain; Denis Castillo Pareja; Abraham J. Vaisberg; Patrice Le Pape

doi:10.1016/j.ejmech.2015.09.002

Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines

Pascal Marchand
, Marc Antoine Bazin
, Fabrice Pagniez
, Guillaume Rivière
, Lizeth Bodero
, Sophie Marhadour
, Marie Renée Nourrisson
, Carine Picot
, Sandrine Ruchaud
, Stéphane Bach
, Blandine Baratte
, Michel Sauvain
, Denis Castillo Pareja
, Abraham J. Vaisberg
, Patrice Le Pape

School of Science and Engineering

UFR des Sciences Pharmaceutiques et Biologiques
Pierre and Marie Curie University Paris 06
Convenio IRD-PeruPetro
Université de Toulouse
Universidad Peruana Cayetano Heredia

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

31 Scopus citations

Abstract

A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity against the promastigote and the amastigote forms of Leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3T3 mouse fibroblast cells. Through LmCK1 inhibition assay, investigations of the putative molecular target of these promising antileishmanial compounds will be discussed.

Original language	English
Pages (from-to)	381-395
Number of pages	15
Journal	European Journal of Medicinal Chemistry
Volume	103
DOIs	https://doi.org/10.1016/j.ejmech.2015.09.002
State	Published - 20 Oct 2015

Keywords

Antileishmanial activity
Casein kinase 1
Direct arylation
Imidazo[1 2-a]pyrazines

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10.1016/j.ejmech.2015.09.002

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Marchand, P., Bazin, M. A., Pagniez, F., Rivière, G., Bodero, L., Marhadour, S., Nourrisson, M. R., Picot, C., Ruchaud, S., Bach, S., Baratte, B., Sauvain, M., Pareja, D. C., Vaisberg, A. J., & Le Pape, P. (2015). Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines. European Journal of Medicinal Chemistry, 103, 381-395. https://doi.org/10.1016/j.ejmech.2015.09.002

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title = "Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines",

abstract = "A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity against the promastigote and the amastigote forms of Leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3T3 mouse fibroblast cells. Through LmCK1 inhibition assay, investigations of the putative molecular target of these promising antileishmanial compounds will be discussed.",

keywords = "Antileishmanial activity, Casein kinase 1, Direct arylation, Imidazo[1 2-a]pyrazines",

author = "Pascal Marchand and Bazin, \{Marc Antoine\} and Fabrice Pagniez and Guillaume Rivi{\`e}re and Lizeth Bodero and Sophie Marhadour and Nourrisson, \{Marie Ren{\'e}e\} and Carine Picot and Sandrine Ruchaud and St{\'e}phane Bach and Blandine Baratte and Michel Sauvain and Pareja, \{Denis Castillo\} and Vaisberg, \{Abraham J.\} and \{Le Pape\}, Patrice",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Masson SAS.",

year = "2015",

month = oct,

day = "20",

doi = "10.1016/j.ejmech.2015.09.002",

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Marchand, P, Bazin, MA, Pagniez, F, Rivière, G, Bodero, L, Marhadour, S, Nourrisson, MR, Picot, C, Ruchaud, S, Bach, S, Baratte, B, Sauvain, M, Pareja, DC, Vaisberg, AJ & Le Pape, P 2015, 'Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines', European Journal of Medicinal Chemistry, vol. 103, pp. 381-395. https://doi.org/10.1016/j.ejmech.2015.09.002

TY - JOUR

T1 - Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines

AU - Marchand, Pascal

AU - Bazin, Marc Antoine

AU - Pagniez, Fabrice

AU - Rivière, Guillaume

AU - Bodero, Lizeth

AU - Marhadour, Sophie

AU - Nourrisson, Marie Renée

AU - Picot, Carine

AU - Ruchaud, Sandrine

AU - Bach, Stéphane

AU - Baratte, Blandine

AU - Sauvain, Michel

AU - Pareja, Denis Castillo

AU - Vaisberg, Abraham J.

AU - Le Pape, Patrice

PY - 2015/10/20

Y1 - 2015/10/20

N2 - A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity against the promastigote and the amastigote forms of Leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3T3 mouse fibroblast cells. Through LmCK1 inhibition assay, investigations of the putative molecular target of these promising antileishmanial compounds will be discussed.

AB - A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity against the promastigote and the amastigote forms of Leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3T3 mouse fibroblast cells. Through LmCK1 inhibition assay, investigations of the putative molecular target of these promising antileishmanial compounds will be discussed.

KW - Antileishmanial activity

KW - Casein kinase 1

KW - Direct arylation

KW - Imidazo[1 2-a]pyrazines

UR - https://www.scopus.com/pages/publications/84941651532

U2 - 10.1016/j.ejmech.2015.09.002

DO - 10.1016/j.ejmech.2015.09.002

M3 - Artículo

C2 - 26383125

AN - SCOPUS:84941651532

SN - 0223-5234

VL - 103

SP - 381

EP - 395

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Synthesis, antileishmanial activity and cytotoxicity of 2,3-diaryl- and 2,3,8-trisubstituted imidazo[1,2-a]pyrazines

Abstract

Keywords

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