Organometallic conjugates of the drug sulfadoxine for combatting antimicrobial resistance

Research output: Contribution to journalArticlepeer-review

Authors

  • P. Chellan
  • A. S. Duffy
  • J. A. Triccas
  • C. Tam
  • L. W. Cheng
  • J. Liu
  • K. M. Land
  • G. J. Clarkson
  • P. J. Sadler

Colleges, School and Institutes

Abstract

Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N,N'‐chelated pyridylimino‐ or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by x‐ray crystallography. Rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10 ‐ 2.0 µM in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes), but were only moderately active towards Trichomonas vaginalis. They were active in both the asexual blood stage and the sexual late stage gametocyte assays, whereas the clinical parent drug, sulfadoxine, was inactive. Five complexes were moderately active against Mycobacterium tuberculosis (IC50 < 6.3 µM), whereas sulfadoxine showed no antitubercular activity. An increase in the size of both the Cpx ligand and the aromatic imino substituent increased hydrophobicity, which resulted in an increase in antiplasmodial activity.

Details

Original languageEnglish
JournalChemistry: A European Journal
Early online date13 Apr 2018
Publication statusE-pub ahead of print - 13 Apr 2018

Keywords

  • organometallic , sulfadrug , antiparasitic , antitubercular