Synthesis, characterization and pharmacological evaluation of ferrocenyl azines and their rhodium(I) complexes

• A series of ferrocenyl salicylaldimines and their corresponding Rh(I) complexes were prepared.
• The compounds were characterized using nuclear magnetic resonance spectroscopy, infrared spectroscopy and mass spectrometry.
• The compounds exhibited moderate activity against the NF54 and K1 strains of Plasmodium falciparum.
• The complexes exhibited enhanced activities compared to the ferrocenyl salicylaldimine ligands.
• Moderate antiparasitic activity was observed against Trichomonas vaginalis for all compounds.

Ferrocenyl azines containing salicylaldimine motifs were prepared by Schiff-base condensation of salicylaldehyde hydrazones and (dimethylamino)methyl ferrocenecarboxaldehyde. Their corresponding Rh(I) complexes were prepared by reaction of the various ferrocenyl azines with [RhCl(COD)]2 (where COD = 1,5-cyclooctadiene) to yield heterobimetallic complexes. The compounds were characterized using standard spectroscopic and analytical techniques. The characterization data suggests that the ferrocenyl azine acts as a bidentate donor. The rhodium(I) centre binds to the imine nitrogen and phenolic oxygen of the salicylaldimine, forming a neutral complex. The compounds were screened against the NF54 chloroquine-sensitive (CQS) and K1 chloroquine-resistant (CQR) strains of Plasmodium falciparum. The ferrocene-containing salicylaldimines exhibited weak to moderate activity across both parasite strains. The heterometallic complexes exhibited enhanced activity compared to the ferrocenyl azines in both strains. Most of the compounds exhibited enhanced activity in the resistant strain compared to the sensitive strain. Inhibition of haemozoin formation was considered as a possible mechanism of action of these compounds and indeed they exhibited β-haematin inhibition activity, albeit weaker than chloroquine. All compounds were also screened against the G3 strain of Trichomonas vaginalis. The compounds inhibited no more than 50% parasite growth at the tested concentration. One complex exhibited moderate cytotoxicity against WHCO1 oesophageal cancer cells.

A series of ferrocenyl azines containing salicylaldimine motifs and their corresponding complexes were synthesised and characterised using standard spectroscopic and analytical techniques. These complexes display moderate activity against Plasmodium falciparum chloroquine-sensitive and chloroquine-resistant strains. Furthermore, the complexes exhibited β-haematin inhibition activity, as a possible mechanism of action.Figure optionsDownload as PowerPoint slide