Synthesis, Crystal Structure, Cytotoxicity, and Mechanism of Action of ZnII, MnII, and FeIII Complexes with 6-Hydroxyloxoisoaporphine

Abstract

Complexes [Zn(L)2(H2O)] (1), [Mn(L)2(CH3OH)2] (2), and [Fe(L)2(CH3OH)Cl] (3) (H–L = 6-hydroxyloxoisoaporphine) were synthesized and characterized. Complex 1 is a five-coordinate distorted tetragonal pyramid, whereas complexes 2 and 3 are six-coordinate distorted octahedral structures. Complexes 1–3 exhibited selective cytotoxicity against MGC80-3, Hep-G2, BEL-7404, and T-24 cells, with IC50 values in the range of 8.19–15.98 µm, and low cytotoxicity to HL-7702 cells. T-24 was the tumor cell most sensitive to complexes 1–3. Complexes 1–3 induced T-24 cell arrest in the G1 and G2/M phases, which led to the upregulation of p27, CDK2, p53, and p21, and downregulation of Cyclin E, Chk1, CDC25A, and Chk2. Complexes 1–3 triggered apoptosis in T-24 cells by a mitochondrial-dysfunction pathway. The interaction of complexes 1–3 with DNA occurs most likely by means of an intercalation and cleavage mode.