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

Sophie Marhadour (1, 2) , Pascal Marchand (2) , Fabrice Pagniez (2) , Marc-Antoine Bazin (2) , Carine Picot (2) , Olivier Lozach (3) , Sandrine Ruchaud (4) , Maud Antoine , Laurent Meijer (5) , Najma Rachidi (6) , Patrice Le Pape (7, 2)

1 Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
2 IICiMed - Cibles et Médicaments des Infections et de l'Immunité
3 SBR - Station biologique de Roscoff = Roscoff Marine Station
4 AD2M - Adaptation et diversité en milieu marin
5 MCT - Molécules et cibles thérapeutiques
6 Parasitologie moléculaire et Signalisation
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes

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.

Mots clés: Antileishmanial activity; 2; 3-Diarylimidazo[1; 2-a]pyridines; Direct arylation; Lipophilicity; Casein kinase 1; Antileishmanial activity 2 3-Diarylimidazo[1 2-a]pyridines Direct arylation Lipophilicity Casein kinase 1; Antileishmanial activity 2; 2-a]pyridines Direct arylation Lipophilicity Casein kinase 1

Domaines: Sciences du Vivant [q-bio]; Chimie; Pharmacologie; Toxicologie

Sophie Marhadour, Pascal Marchand, Fabrice Pagniez, Marc-Antoine Bazin, Carine Picot, et al.. Synthesis and biological evaluation of 2,3-diarylimidazo[1,2-a]pyridines as antileishmanial agents. European Journal of Medicinal Chemistry, 2012, 58, pp.543-556. ⟨10.1016/j.ejmech.2012.10.048⟩. ⟨hal-03882013⟩