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

Research aimed at enhancing the efficacy of organometallic complexes againstcancer, has shown that attaching bio‐active molecules to (metallo)drugs oftenenhances their biological properties. New salicylaldimine and 2‐pyridylimineligands (L2 and L3), containing a bio‐active acridine scaffold, were synthesizedand complexed to Rh(III), Ir(III), Ru(II) and Os(II) metal ion centers. The resultingacridine‐containing half‐sandwich complexes have been characterized fully byelemental analysis, FT‐IR and NMR spectroscopy, HR‐ESI mass spectrometry aswell as single crystal X‐ray diffraction, for the Rh(III) N^N bidentate complex[RhCp*Cl(L3)][BPh4]. The antiproliferative activity of the ligands (L2 and L3)and complexes (C1 to C9) were evaluated in vitro against human promyelocytic leukemiacells (HL60) and normal skin fibroblast cells (FG0). The compounds exhibitgood activities against HL60 cells and are consistently selective towards cancerouscells over non‐tumorous cells. This study demonstrates the potential of such hybridcompounds 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 complexwith 5’‐GMP found on DNA backbone