Synthesis, Docking, In Vitro and In Vivo Antimalarial Activity of Hybrid 4-aminoquinoline-1,3,5-triazine Derivatives Against Wild and Mutant Malaria Parasites

Chem Biol Drug Des. 2015 Sep;86(3):265-71. doi: 10.1111/cbdd.12490. Epub 2015 Jan 16.

Abstract

A new series of hybrid 4-aminoquinoline-1,3,5-triazine derivatives was synthesized by a four-step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (3D-7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P. falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) type pf-DHFR-TS to highlight the structural features of hybrid molecules.

Keywords: 1,3,5-triazine; aminoquinoline; antimalarial; docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemistry*
  • Aminoquinolines / pharmacology*
  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Malaria / drug therapy
  • Molecular Docking Simulation / methods
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship
  • Triazines / chemistry*
  • Triazines / pharmacology*

Substances

  • Aminoquinolines
  • Antimalarials
  • Triazines
  • 4-aminoquinoline