1,2-Diphenoxiethane salts as potent antiplasmodial agents

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2485-2489. doi: 10.1016/j.bmcl.2018.05.060. Epub 2018 May 31.

Abstract

In this article we present a series of non-cytotoxic potent human choline kinase (CK) inhibitors that exhibit nanomolar antiplasmodial activity in vitro. The most active antiplasmodial compounds, 10a-b, bearing a pyridinium cationic head were inactive against CK, while compounds 10g and 10j with a quinolinium moiety exhibit moderate inhibition of both the parasite and the enzyme. The results point towards an additional mechanism of action unrelated to CK inhibition that remains to be established.

Keywords: Antiplasmodial agents; Non-cytotoxic; Plasmodium falciparum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Choline Kinase / antagonists & inhibitors*
  • Choline Kinase / metabolism
  • Dose-Response Relationship, Drug
  • Ethane / analogs & derivatives*
  • Ethane / chemical synthesis
  • Ethane / chemistry
  • Ethane / pharmacology
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Salts / chemical synthesis
  • Salts / chemistry
  • Salts / pharmacology
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Biphenyl Compounds
  • Protein Kinase Inhibitors
  • Salts
  • Choline Kinase
  • Ethane
  • 1,2-diphenoxyethane