Synthesis, X-ray structure, in vitro HIV and kinesin Eg5 inhibition activities of new arene ruthenium complexes of pyrimidine analogs

Abstract

Three new ruthenium(II)-arene complexes of the general formula [{(η6-p-cymene)Ru(L)}2](Cl)2), where L are monastrol (L1), ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate (L2) or its 4-bromophenyl analog (L3), have been synthesized and characterized by elemental analysis, 1H, 13C, and 2-D NMR spectroscopy. The X-ray diffraction study of complex 1 showed the presence of a dicationic diruthenium complex where two thioxopyrimidines act as tridentate μ,κN:κ2S ligand, bridging two Ru ions through the pyrimidine nitrogen and sulfur atoms. All new complexes were evaluated in vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells using MTT assay. Additionally, complexes 1–3 were screened for their inhibitory activity against the ATPase enzyme and the motor-protein Kinesin Eg5. Complex 1 was found to inhibit microtubule-stimulated ATPase activity of kinesin of IC50 = 30 μM (monastrol, IC50 = 10 μM).