Stringer T., Guzgay H., Combrinck J.M., Hopper M., Hendricks D.T., Smith P.J., Land K.M., Egan T.J., Smith G.S.
Department of Chemistry, University of Cape Town, Rondebosch, South Africa; Division of Medical Biochemistry, University of Cape Town, Rondebosch, South Africa; Division of Pharmacology, Department of Medicine, University of Cape Town Medical School, Observatory, South Africa; Department of Biological Sciences, University of the Pacific, Stockton, CA, United States
Stringer, T., Department of Chemistry, University of Cape Town, Rondebosch, South Africa; Guzgay, H., Division of Medical Biochemistry, University of Cape Town, Rondebosch, South Africa; Combrinck, J.M., Department of Chemistry, University of Cape Town, Rondebosch, South Africa, Division of Pharmacology, Department of Medicine, University of Cape Town Medical School, Observatory, South Africa; Hopper, M., Department of Biological Sciences, University of the Pacific, Stockton, CA, United States; Hendricks, D.T., Division of Medical Biochemistry, University of Cape Town, Rondebosch, South Africa; Smith, P.J., Division of Pharmacology, Department of Medicine, University of Cape Town Medical School, Observatory, South Africa; Land, K.M., Department of Biological Sciences, University of the Pacific, Stockton, CA, United States; Egan, T.J., Department of Chemistry, University of Cape Town, Rondebosch, South Africa; Smith, G.S., Department of Chemistry, University of Cape Town, Rondebosch, South Africa
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)]<inf>2</inf> (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. © 2015 Elsevier B.V. All rights reserved.