Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(II) and rhodium(III) thiosemicarbazone complexes

Muneebah Adams; Carmen de Kock; Peter J. Smith; Kirkwood M. Land; Nicole Liu; Melissa Hopper; Allyson Hsiao; Andrew R. Burgoyne; Tameryn Stringer; Mervin Meyer; Lubbe Wiesner; Kelly Chibale; Gregory S. Smith

doi:10.1039/C4DT03234A

Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(ii) and rhodium(iii) thiosemicarbazone complexes†

Muneebah Adams,^a Carmen de Kock,^b Peter J. Smith,^b Kirkwood M. Land,^c Nicole Liu,^c Melissa Hopper,^c Allyson Hsiao,^c Andrew R. Burgoyne,^a Tameryn Stringer,^a Mervin Meyer,^d Lubbe Wiesner,^b Kelly Chibale^aef and Gregory S. Smith*^a

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* Corresponding authors

^a Department of Chemistry, University of Cape Town, Rondebosch 7701, Cape Town, South Africa
E-mail: Gregory.Smith@uct.ac.za
Fax: +27-21-6505195

^b Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa

^c Department of Biological Sciences, University of the Pacific, Stockton, CA 95211, USA

^d Department of Biotechnology, University of the Western Cape, Bellville 7535, Cape Town, South Africa

^e Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa

^f South African Medical Research Council Drug Discovery & Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa

Abstract

A series of ferrocenyl- and aryl-functionalised organosilane thiosemicarbazone compounds was obtained via a nucleophilic substitution reaction with an amine-terminated organosilane. The thiosemicarbazone (TSC) ligands were further reacted with either a ruthenium dimer [(η^6-iPrC₆H₄Me)Ru(μ-Cl)Cl]₂ or a rhodium dimer [(Cp*)Rh(μ-Cl)Cl]₂ to yield a series of cationic mono- and binuclear complexes. The thiosemicarbazone ligands, as well as their metal complexes, were characterised using NMR and IR spectroscopy, and mass spectrometry. The molecular structure of the binuclear ruthenium(II) complex was determined by single-crystal X-ray diffraction analysis. The thiosemicarbazones and their complexes were evaluated for their in vitro antiplasmodial activities against the chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) Plasmodium falciparum strains, displaying activities in the low micromolar range. Selected compounds were screened for potential β-haematin inhibition activity, and it was found that two Rh(III) complexes exhibited moderate to good inhibition. Furthermore, the compounds were screened for their antitrichomonal activities against the G3 Trichomonas vaginalis strain, revealing a higher percentage of growth inhibition for the ruthenium and rhodium complexes over their corresponding ligand.

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Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(ii) and rhodium(iii) thiosemicarbazone complexes†

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Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(II) and rhodium(III) thiosemicarbazone complexes

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