2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2298-301. doi: 10.1016/j.bmcl.2015.04.030. Epub 2015 Apr 16.

Abstract

Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model.

Keywords: Cyclin-dependent kinase; Inhibitor; Leishmania; Purine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology
  • Binding Sites
  • Leishmania donovani / drug effects*
  • Leishmania major / drug effects*
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-crk / antagonists & inhibitors*
  • Purines / chemistry*
  • Purines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antiprotozoal Agents
  • Proto-Oncogene Proteins c-crk
  • Purines