Synthesis, spectroscopic characterization, photochemical and photophysical properties and biological activities of ruthenium complexes with mono- and bi-dentate histamine ligand

Abstract

The monodentate cis-[Ru( phen) 2 (hist) 2 ] 2+ 1R and the bidentate cis-[Ru( phen) 2 (hist)] 2+ 2A complexes were prepared and characterized using spectroscopic Cell uptake of the complexes into HeLa cells was detected by fluorescence confocal microscopy. Overall, the observation of a luminescent complex that penetrates the cell wall and has low cytotoxicity, but is reactive photochemically, releasing histamine when irradiated with visible light, are interesting features for application of these complexes as phototherapeutic agents.

Organoruthenium Prodrugs as a New Class of Cholinesterase and Glutathione‐S‐Transferase Inhibitors

“…The potency of C1 a toward the cholinesterases was also in a pharmaceutically interesting range, with IC 50 values of 5.0, 25.1, and 7.5 μ m against electric eel (ee)AChE, human (h)AChE and horse serum BChE, respectively. This IC 50 range is similar to that of other ruthenium‐based cholinesterase inhibitors, where the IC 50 values have been reported to be in the range of 0.2 μ m to 50 μ m . The inhibition of all three tested cholinesterases was of a reversible competitive type.…”

“…Most of the recent data in the field of ruthenium‐based cholinesterase inhibitors are built on those of Dwyer and Gyarfas from the early 1950s, and involve the tris‐phenanthroline ruthenium(II) complex . A structural analysis of compounds in more recent studies showed that the compounds investigated share structural similarities with the parent Dwyer complex, whereby the Ru II ion is either bound to three identical phenanthroline derivatives, as [Ru(phen‐R) 3 ] 2+ , or ruthenium(II) is coordinated by two phenanthroline ligands and either two monodentate N ‐ligands or one bidentate N , N ‐ligand, as [Ru(phen) 2 N 1 N 2 ] 2+ . From the chemical point of view, these compounds are considered inert for substitutions under physiological conditions, and can interact with target macromolecules through the side groups of the ligand substructures by intercalation or through electrostatic, covalent, or supramolecular interactions.…”

“…The inhibition of GSTs by ruthenium compounds is already well established . Furthermore, more recently, and now 66 years after the first report by Dwyer and Gyarfas in 1952, ruthenium‐based complexes have been rediscovered as potential anti‐cholinesterase agents with interesting pharmaceutical potential …”

Fine Tuning of Cholinesterase and Glutathione-S-Transferase Activities by Organoruthenium(II) Complexes

“…The repeated testing of the inhibitory potential of complex 1 towards the hrAChE lot used in the present study confirmed that the observed differences were due to an enzyme structural defect, and not to the different monodentate Z ligands (i.e., Cl – , Br – , I – , pta). Both the Br – and I – analogues inhibited the ChEs in a pharmaceutically interesting low micromolar range [ 51 ] and were comparable to other ruthenium-based cholinesterase inhibitors, with IC 50 values reported in the range of 0.2 μM to 50 μM [ 11 , 54 , 55 , 56 , 57 ]. Inhibition of all three ChEs was reversible and competitive, with K i values in the low micromolar range ( Figures S1–S2 ).…”

Structural Isomerism and Enhanced Lipophilicity of Pyrithione Ligands of Organoruthenium(II) Complexes Increase Inhibition on AChE and BuChE

“…However, as mentioned, cholinergic system seems to be the most promising therapeutic field to combat AD. Some ruthenium complexes, mainly ruthenium(II) polypyridyl compounds, have also been examined as AChE inhibitors [ 16 , 17 , 18 ], and some of them additionally inhibit Aβ aggregation [ 19 , 20 , 21 ]. Recently, we have reported a potent chlorido organoruthenium(II) complex with pyrithione 1a ( Scheme 1 ) ( a —pyrithione, also 1-hydroxypyridine-2(1 H )-thione or 2-mercaptopyridine N -oxide) [ 22 ], which is an excellent reversible competitive inhibitor of three ChEs, namely electric eel AChE (eeAChE), human AChE (hAChE), and horse serum BuChE (hsBuChE) with low micromolar IC 50 values (5.01 µM, 25.06 µM, and 7.52 µM, respectively).…”