Acridine‐containing Ru^II, Os^II, Rh^III and Ir^III Half‐Sandwich Complexes: Synthesis, Structure and Antiproliferative Activity

Abstract

Research aimed at enhancing the efficacy of organometallic complexes against cancer, has shown that attaching bio-active molecules to (metallo)drugs often enhances their biological properties. New salicylaldimine and 2-pyridylimine ligands (L2 and L3), containing a bio-active acridine scaffold, were synthesized and complexed to Rh(III), Ir(III), Ru(II) and Os(II) metal ion centers. The resulting acridine-containing half-sandwich complexes have been characterized fully by elemental analysis, FT-IR and NMR spectroscopy, HR-ESI mass spectrometry as well as single crystal X-ray diffraction, for the Rh(III) N^N bidentate complex [RhCp*Cl(L3)][BPh 4 ]. The antiproliferative activity of the ligands (L2 and L3) and complexes (C1 to C9) were evaluated in vitro against human promyelocytic leukemia cells (HL60) and normal skin fibroblast cells (FG0). The compounds exhibit good activities against HL60 cells and are consistently selective towards cancerous cells over non-tumorous cells. This study demonstrates the potential of such hybrid compounds to target cancer cells specifically. The most active complex, [RhCp*Cl(L2)], exhibited binding to DNA model guanosine-5'-monophosphate (5'-GMP) which suggests a mode of action involving interaction of the complex with 5'-GMP found on DNA backbone.

New Triazolyl N^N Bidentate Rh(III), Ir(III), Ru(II) and Os(II) Complexes: Synthesis and Characterization, Probing Possible Relations between Cytotoxicity with Transfer Hydrogenation Efficacy and Interaction with Model Biomolecules

“…Half-Sandwich complexes such as [(η 6 -arene)M(L)Cl] + have demonstrated good anticancer activity through multimodal binding with DNA [ 14 , 15 ]. Interestingly, one such complex, RAPTA-C, is an antimetastatic, antitumoral and antiangiogenic drug candidate with the potential of reaching clinical evaluation [ 16 ].…”

Metal Complexes in Cancer Treatment: Journey So Far

“…Their anti‐proliferative activity was evaluated on the HL‐60 (blood cancer) cell lines, and the effective results were obtained ( Table 35). Compound 67 exhibited most effective anti‐proliferative activity [134] …”

The interaction of half-sandwich (η5-Cp*)Rh(III) cation with histidine containing peptides and their ternary species with (N,N) bidentate ligands

“…Following the work made in the Sadler and Dyson research groups, a number of further (arene)Ru(II)-based compounds have been identified as potential candidates for clinical development [1][2][3][4][5][6][7]. Although, considerably less experimental data have been published for the isoelectronic (arene)Rh(III) compounds, several (η 5 -Cp*)Rh(III) complexes exhibit higher in vitro activity than the related Ru(II) complexes or even cisplatin, at least against selected cancer cell lines [8][9][10][11][12][13][14][15][16][17]. In addition, its optimal ligand exchange kinetics make (η 5 -Cp*)Rh(III) cation suitable drug delivery system for cytotoxins that are too toxic to be delivered directly, or have poor pharmacokinetics, such as curcumin [18].…”