Antileishmanial activity of quinazoline derivatives: synthesis, docking screens, molecular dynamic simulations and electrochemical studies

Eur J Med Chem. 2015 Mar 6:92:314-31. doi: 10.1016/j.ejmech.2014.12.051. Epub 2014 Dec 29.

Abstract

A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N(6)-(ferrocenmethyl)quinazolin-2,4,6-triamine (H2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electrochemical studies showed the importance of both the ferrocene and the heterocyclic nucleus to the observed activity. H2 is readily oxidized electrochemically, indicating that the mechanism of action probably involves redox reactions.

Keywords: Antiprotozoan activity; Leishmania mexicana; Quinazoline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrochemical Techniques*
  • Leishmania mexicana / cytology
  • Leishmania mexicana / drug effects*
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Solubility
  • Structure-Activity Relationship

Substances

  • Antiprotozoal Agents