Ruthenium complexes with bioactive ligands are becoming promising substitutes for platinum complexes due to their precise action against various cancers. In the present study, the synthesis of three new arene Ru(II) complexes containing new carbazole-based hydrazone ligands of general formula [(η⁶-benzene)Ru(L)Cl] (1–3; L = carbazolone benzhydrazone ligands), and their anticancer properties are described. The structural characterization of the ligands and their ruthenium complexes has been realized with the aid of elemental analysis, IR, UV-vis, NMR and HR-MS techniques. The molecular structures of all three complexes have been elucidated by single crystal X-ray crystallography and reveal the existence of pseudo-octahedral geometry around the ruthenium. The in vitro cancer cell growth inhibition property of the complexes against A549 (lung carcinoma), A2780 (ovarian adenocarcinoma) and non-cancerous 16HBE (human lung bronchial epithelium) cells were examined by MTT assay. All the complexes display good cytotoxicity towards both of these types of cancer cell compared to the standard drug cisplatin, with low IC₅₀ values. Remarkably, complex 3, which contains an electron-donating substituent, induces a significant reduction of viability in A2780 cells. The inhibition capacity of the complexes towards A2780 cells proliferation was further confirmed using 5-ethynyl-2-deoxyuridine (EdU) assay via minimal DNA synthesis. The result of the acridine orange-ethidium bromide (AO-EB) fluorescent staining assay establishes that the cytotoxicity of the complexes was mediated by apoptosis in cancer cells. Furthermore, flow cytometry using Annexin V-FITC/propidium iodide (PI) double staining determines the quantitative discrimination of early apoptosis by the externalization of phosphatidylserine. In addition, cell cycle distribution indicates that the complexes block the cell cycle progression in the S-phase. The outcome of our investigation shows the promising scope and potency of tailored arene ruthenium complexes for precise cancer chemotherapy beyond platinum drugs.

Ruthenium(II) carbonyl complexes with phosphine-functionalized PNS type thiosemicarbazone ligands [RuCl(CO)(EPh₃)(L)] (1–6) (E = P or As, L = 2-(2-(diphenylphosphino)benzylidene) thiosemicarbazone (PNS-H), 2-(2-(diphenylphosphino)benzylidene)-N-methylthiosemicarbazone (PNS-Me), 2-(2-(diphenylphosphino)benzylidene)-N-phenylthiosemicarbazone (PNS-Ph)) have been synthesized and characterized by elemental analysis and spectroscopy (IR, UV-Vis, ¹H, ¹³C, ³¹P-NMR) as well as ESI mass spectrometry. The molecular structures of complexes 1, 2 and 6 were identified by means of single-crystal X-ray diffraction analysis. The analysis revealed that all the complexes possess a distorted octahedral geometry with the ligand coordinating in a uni-negative tridentate PNS fashion. All the ruthenium complexes (1–6) were tested as catalyst for N-alkylation of heteroaromatic amines with alcohols. Notably, complex 2 was found to be a very efficient and versatile catalyst towards N-alkylation of a wide range of heterocyclic amines with alcohols. Complex 2 can also catalyze the direct amination of 2-nitropyridine with benzyl alcohol to the corresponding secondary amine. Furthermore, a preliminary examination of performance for N,N-dialkylation of diamine showed promising results, giving good conversion and high selectivity. In addition, N-alkylation of ortho-substituted anilines (–NH₂, –OH and –SH) led to the one-pot synthesis of 2-aryl substituted benzimidazoles, benzoxazoles and benzothiazoles, also revealing the catalytic activity of complex 2.

Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds 1d and 3c demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized “soft” donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the N,N,S donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of 1d and 3c that warrants further examination.

A series of coumarin-substituted 1,2,4-triazolium salts and their respective silver– and gold– N-heterocyclic carbene complexes have been reported. The complexes displayed promising anticancer activity with GI₅₀ values of up to 0.354 μM and 8.5983 μM against MCF 7 and HT-29 cell lines, respectively.