Pharmacophore-guided optimization of the hit compound CTN1122 in the design of promising imidazo[1,2-<i>a</i>]pyrazine derivatives targeting the casein kinase 1 for antileishmanial therapy.

ABSTRACT: Our research group identified CTN1122, an imidazo[1,2-a]pyrazine derivative, as a promising antileishmanial agent targeting intramacrophage amastigotes of Leishmania major and Leishmania donovani. CTN1122 selectively inhibits Leishmania casein kinase 1 (L-CK1.2) with a favorable safety profile. Docking studies based on a homology model highlighted key pharmacophoric elements: a 4-pyridyl group at C3, crucial for hydrogen bonding with leucine 90 in the ATP-binding site, and a 4-fluorophenyl moiety at C2, fitting into a hydrophobic pocket. In order to validate these findings, 14 analogs were synthesized with targeted modifications on the imidazo[1,2-a]pyrazine core structure. Three probed the C8 position, three evaluated the impact of C2 substitution, six a

SUBMITTER: Tisseur L 

PROVIDER: S-EPMC12177573 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature