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

• DOI: 10.1016/j.ejmech.2012.10.048
• Publication Date: 2012-11-02T21:31:59Z
• Authors: Sophie Marhadour; Pascal Marchand; Fabrice Pagniez; Marc-Antoine Bazin; Carine Picot; Olivier Lozach; Sandrine Ruchaud; Maud Antoine; Laurent Meijer; Najma Rachidi; Patrice Le Pape
• Keywords: Models, Molecular; Pyridines; [SDV]Life Sciences [q-bio]; Casein kinase 1; 2; Antiprotozoal Agents; Antineoplastic Agents; Direct arylation; 01 natural sciences; Structure-Activity Relationship; Parasitic Sensitivity Tests; 615; Lipophilicity; [CHIM] Chemical Sciences; [CHIM]Chemical Sciences; Humans; Protein Kinase Inhibitors; Protein Kinase C; Antileishmanial activity 2; Cell Proliferation; Leishmania major; Dose-Response Relationship, Drug; Molecular Structure; Casein Kinase I; Antileishmanial activity; 540; 0104 chemical sciences; 3. Good health; [SDV] Life Sciences [q-bio]; [SDV.TOX] Life Sciences [q-bio]/Toxicology; Antileishmanial activity 2 3-Diarylimidazo[1 2-a]pyridines Direct arylation Lipophilicity Casein kinase 1; [SDV.TOX]Life Sciences [q-bio]/Toxicology; 3-Diarylimidazo[1; [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; 2-a]pyridines Direct arylation Lipophilicity Casein kinase 1; Drug Screening Assays, Antitumor; 2-a]pyridines; HeLa Cells

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.