Maxime D. Crozet

Targeting the human parasite Leishmania donovani: Discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series

We report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of Leishmania donovani, J774A.1 murine and HepG2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). New derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying both a high potency (IC50=1.8 μM) and a good selectivity index, in comparison with three antileishmanial reference drug-compounds (amphotericin B, miltefosine and pentamidine). Moreover, lead-compound 44 also exhibits good in vitro activity against the intracellular amastigote stage of L. donovani. Thus, the 6-halo-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine scaffold appears as a new promising selective antileishmanial pharmacophore, especially when substituted at position 8 by a bromine atom.

Rapid synthesis of new 2-methyl-7-nitro-5-substituted-2,3-dihydroimidazo[5,1-b]oxazole as potential antibacterial drugs through one-pot cyclization and Suzuki–Miyaura coupling

ABSTRACT Original 2-methyl-7-nitro-5-substituted-2,3-dihydroimidazo[5,1-b]oxazoles were prepared by reacting 1-(2,5-dibromo-4-nitro-1H-imidazol-1-yl)propan-2-ol and various arylboronic acids through “one-pot” cyclization and Suzuki–Miyaura reactions under microwave irradiation. GRAPHICAL ABSTRACT