Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents

Bioorg Med Chem Lett. 2009 Dec 15;19(24):6996-9. doi: 10.1016/j.bmcl.2009.10.010. Epub 2009 Oct 29.

Abstract

There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malaria after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride. The series of new hybrid 9-anilinoacridine triazines were evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of Plasmodium falciparum and their cytotoxicity were determined on VERO cell line. Of the evaluated compounds, two compounds 17 (IC(50)=4.21 nM) and 22 (IC(50)=4.27 nM) displayed two times higher potency than CQ (IC(50)=8.15 nM). Most of the compounds showed fairly high selectivity index. The compounds 13 and 29 displayed >96.59% and 98.73% suppression, respectively, orally against N-67 strain of Plasmodium yoelii in swiss mice at dose 100 mg/kg for four days.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amsacrine / analogs & derivatives*
  • Amsacrine / chemical synthesis
  • Amsacrine / pharmacology
  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • Mice
  • Plasmodium falciparum / drug effects*
  • Triazines / chemical synthesis*
  • Triazines / pharmacology

Substances

  • Antimalarials
  • Triazines
  • Amsacrine
  • 9-anilinoacridine