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

Three new ruthenium(II)-arene complexes of the general formula [{((6)-p-cymene)Ru(L)}(2)](Cl)(2)), where L are monastrol (L-1), ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-pyrimidine-5-carboxylate (L-2) or its 4-bromophenyl analog (L-3), have been synthesized and characterized by elemental analysis, H-1, C-13, 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 ,N:S-2 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=30M (monastrol, IC50=10M). [GRAPHICS] .