Synthesis and biological evaluation of 2,3-diarylimidazo[1,2-a]pyridines as antileishmanial agents

Sophie Marhadour; Pascal Marchand; Fabrice Pagniez; Marc-Antoine Bazin; Carine Picot; Olivier Lozach; Sandrine Ruchaud; Maud Antoine; Laurent Meijer; Najma Rachidi; Patrice Le Pape

doi:10.1016/j.ejmech.2012.10.048

Synthesis and biological evaluation of 2,3-diarylimidazo[1,2-a]pyridines as antileishmanial agents

Eur J Med Chem. 2012 Dec:58:543-56. doi: 10.1016/j.ejmech.2012.10.048. Epub 2012 Nov 2.

Authors

Sophie Marhadour¹, Pascal Marchand, Fabrice Pagniez, Marc-Antoine Bazin, Carine Picot, Olivier Lozach, Sandrine Ruchaud, Maud Antoine, Laurent Meijer, Najma Rachidi, Patrice Le Pape

Affiliation

¹ Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICiMed UPRES EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.

PMID: 23164660
DOI: 10.1016/j.ejmech.2012.10.048

Abstract

A novel series of 2,3-diarylimidazo[1,2-a]pyridines was synthesized and evaluated for their antileishmanial activities. Four derivatives exhibited good activity against the promastigote and intracellular amastigote stages of Leishmania major, coupled with a low cytotoxicity against the HeLa human cell line. The impact of compound lipophilicity on antiparasitic activities was investigated by Log D comparison. Although LmCK1 could be the parasitic target for three compounds (13, 18, 21), the inhibition of another target is under study to explain the antileishmanial effect of the most promising compounds.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Antiprotozoal Agents / chemical synthesis
Antiprotozoal Agents / chemistry
Antiprotozoal Agents / pharmacology*
Casein Kinase I / antagonists & inhibitors
Casein Kinase I / metabolism
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Leishmania major / drug effects*
Leishmania major / enzymology
Models, Molecular
Molecular Structure
Parasitic Sensitivity Tests
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / metabolism
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Antiprotozoal Agents
Protein Kinase Inhibitors
Pyridines
Casein Kinase I
Protein Kinase C
imidazo(1,2-a)pyridine