In vitro identification of imidazo[1,2-a]pyrazine-based antileishmanial agents and evaluation of L. major casein kinase 1 inhibition

Leishmaniasis constitutes a severe public health problem, with an estimated prevalence of 12 million cases. This potentially fatal disease has worldwide distribution and in 2012, the Visceral (VL) was declared as new emerging Europe, mainly due to global warming, expected important impact. The available treatments are toxic, costly or lead parasite resistance, thus there is urgent need for drugs mechanism action. Previously, we reported discovery CTN1122 , potent imidazo[1,2- ]pyrazine-based antileishmanial hit compound targeting L-CK1.2 at low micromolar ranges. Here, described structurally related, safe selective compounds endowed antiparasitic properties, better than miltefosine, reference therapy by oral route. homology model gave first structural explanations role 4-pyridyl ( ) 2-aminopyrimidin-4-yl (compound 21 moieties, position 3 central core, nanomolar inhibition, whereas N -methylpyrazole derivative 11 remained inactive against kinase. • 13 ]pyrazines related were synthesized antileishmanials most promising displayed range potency VL. inhibitory activity. 6 showed inhibition.