Acridine‐containing RuII, OsII, RhIII and IrIII Half‐Sandwich Complexes: Synthesis, Structure and Antiproliferative Activity

Research aimed at enhancing the efficacy of organometallic complexes against<br>cancer, has shown that attaching bio‐active molecules to (metallo)drugs often<br>enhances their biological properties. New salicylaldimine and 2‐pyridylimine<br>ligands (L2 and L3), containing a bio‐active acridine scaffold, were synthesized<br>and complexed to Rh(III), Ir(III), Ru(II) and Os(II) metal ion centers. The resulting<br>acridine‐containing half‐sandwich complexes have been characterized fully by<br>elemental analysis, FT‐IR and NMR spectroscopy, HR‐ESI mass spectrometry as<br>well as single crystal X‐ray diffraction, for the Rh(III) N^N bidentate complex<br>[RhCp*Cl(L3)][BPh4]. The antiproliferative activity of the ligands (L2 and L3)<br>and complexes (C1 to C9) were evaluated in vitro against human promyelocytic leukemia<br>cells (HL60) and normal skin fibroblast cells (FG0). The compounds exhibit<br>good activities against HL60 cells and are consistently selective towards cancerous<br>cells over non‐tumorous cells. This study demonstrates the potential of such hybrid<br>compounds to target cancer cells specifically. The most active complex,<br>[RhCp*Cl(L2)], exhibited binding to DNA model guanosine‐5’‐monophosphate<br>(5’‐GMP) which suggests a mode of action involving interaction of the complex<br>with 5’‐GMP found on DNA backbone