Abstract
RuII(arene) complexes have emerged as a versatile class of compounds to design metallodrugs as potential treatment for a wide range of diseases including cancer and malaria. They feature modes of action that involve classic DNA binding like platinum anticancer drugs, may covalent binding to proteins, or multimodal biological activity. Herein, we report the synthesis and urease inhibition activity of RuII(arene) complexes of the general formula [RuII(η6-p-cymene)(L)Cl2] and [RuII(η6-p-cymene)(PPh3)(L)Cl]PF6 with S-donor systems (L) based on heterocyclic thiourea derivatives. The compounds were characterized by 1H-, 13C{1H}- and 31P{1H}-NMR spectroscopy, as well as elemental analysis. The crystal structure of [chlorido(η6-p-cymene)(imidazolidine-2-thione)(triphenylphosphine)ruthenium(II)] hexafluorophosphate 11 was determined by X-ray diffraction analysis. A signal in the range 175–183 ppm in the 13C{1H}-NMR spectrum indicates the presence of a thione rather than a thiolate. This observation was also confirmed in the solid state by X-ray diffraction analysis of 11 which shows a C=S bond length of 1.720 Å. The compounds were tested for urease inhibitory activity and the thiourea-derived ligands exhibited moderate activity, whereas their corresponding Ru(arene) complexes were not active.
Highlights
Medicinal inorganic chemistry is a relatively new subject, but an emerging area of research in drug discovery that employs metals as pharmacophores or introduces structural features not achievable with organic structures
The novel complexes 6–10 were obtained in good yields (63%–86%) by stirring two equivalents of the thiourea derivatives I–III with one equivalent of the respective ruthenium dimers 1–3 in dichloromethane or methanol for 2–4 h (Scheme 1)
In the 1H-NMR spectra, the signals originating from protons directly attached to the nitrogen atoms of the thiourea derivatives appeared at δ = 8–12 ppm, depending on the thiourea derivative and the solvent employed for the NMR measurement
Summary
Medicinal inorganic chemistry is a relatively new subject, but an emerging area of research in drug discovery that employs metals as pharmacophores or introduces structural features not achievable with organic structures. Nowadays many metallodrugs are routinely used for the treatment and diagnosis of a variety of diseases. These include gold compounds that are successfully applied as antiarthritic drugs, platinum chemotherapeutics as anticancer agents and gadolinium complexes as MRI contrast agents [1]. Since the discovery of the anticancer agent cisplatin, the design paradigm of metal-based anticancer compounds has largely focused on DNA-targeting metal complexes, resembling the mode of action of cisplatin and derivatives. A variety of metal complexes acting as enzyme inhibitors were developed [2]. A metal ion can either act as a spectator in a kinetically inert complex while its ligands interact with the active site of an enzyme, contributing solely to the overall structure of the inhibitor, or the metal ion can actively participate in the binding event to the enzyme
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