Synthesis, Structures And Cytotoxicity Of Mono-and Dinuclear Rutheniu Marene Complexes Derived From Thiosemicarbazone Ligands

Thiosemicarbazones(TSCs) have attracted considerable attention by chemists and biologists because of their wide range of pharmacological effects. These compounds and their metal complexes have shown marked biological activity,particularly the antitumor activity. At the same time, ruthenium-based complexes have attracted great attention owing to the high activity and low cytotoxity. Therefore,thiosemicarbazides were chosen as ligand to react with aryl ruthenium precursors, to obtain ruthenium complexes with thiosemicarbazide ligand. Moreover, the structures and anticancer activity of these complexes were investigated.1. Synthesis and Characterization of a Series of Ruthenium(II) Arene ComplexesSixteen thiosemicarbazide ligands(L1 ~ L16) were synthesized by reaction of o-Methoxybenzaldehyde, m-Methoxybenzaldehyde, p-Methoxybenzaldehyde,p-fluoro-Benzaldehyde, p-Hydroxybenzaldehyde, 2-Thenaldehyde, Benzaldehyde and Acetophenone with 3-thiosemicarbazide, 4-methyl-3-thiosemicarbazide,4-Ethyl-3-thiosemicarbazide and 4-phenyl-3-thiosemicarbazide respectively.Thirty-one complexes were prepared by reacting [(?6-p-cymene)RuCl2]2 with L1 ~L16, respectively. These complexes were characterized by 1H NMR, 13 CNMR, UV,HR-ESI-MS and elemental analysis. Moreover, the structures of complexes 1a?2a?13a,1b~4b?9b?15b,1c~5c?7c?8c?10c~13c were determined by X- ray single crystal diffraction. Theses complexes have two crystal structures: mononuclear and dinuclear. The stability of these complexes in water was determined by UV spectrum.2. Anticancer Activity of These Ruthenium(II) Arene ComplexesThe in vitro growth antiproliferative activities were evaluated against the SGC-7901 human gastric cancer, KB human squamous cancer, CNE-2 human nasopharyngeal carcinoma cancer, HeLa human Cervical cancer, Hepg2 human liver cancer and HEK-293 T noncancerous cell lines by MTT method, and compared to that of cisplatin, oxaliplatin, and carboplatin, the well-known antitumor agents. A-type complexes exhibited low antiproliferative activities, but B-type complexes exhibit moderate activities, while C-type complexes show the most potent activities. Herein,complex 8c, which possesses IC50 values of 9.2 ± 1.5 ?M, 7.5 ± 0.9 ?M and 7.6 ± 1.0?M, against SCG-7901, CNE-2 and KB cancer cell lines, respectively, shows anticancer activities prior to that of cisplatin, oxaliplatin, and carboplatin.