Structure-activity relationship investigations of leishmanicidal N-benzylcytisine derivatives

Chem Biol Drug Des. 2011 Jul;78(1):183-9. doi: 10.1111/j.1747-0285.2011.01092.x. Epub 2011 May 25.

Abstract

In vitro leishmanicidal activity of 16 N-benzylcytisine derivatives has been evaluated using Leishmania donovani axenic amastigotes. In general, halogen (bromo-, chloro-) derivatives appeared to be more toxic against parasites than their parent compounds. Quantum-chemical calculations helped to recognize certain patterns in the structure of frontier orbitals related to bioactivity of compounds. Thus, the presence of halogen atom is shown to have a significant effect on both distribution and the energy of LUMOs thereby on potent activity that was also confirmed by Quantitative-Structure Activity Relationship (QSAR) analysis. Experimentally and theoretically observed structure-cytotoxicity relationships are described.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / pharmacology*
  • Inhibitory Concentration 50
  • Leishmania donovani / drug effects*
  • Models, Molecular
  • Quantitative Structure-Activity Relationship
  • Quinolizines / chemistry*
  • Quinolizines / pharmacology*

Substances

  • Antiprotozoal Agents
  • Quinolizines