Synthesis and antitumor activities of transition metal complexes of a bis-Schiff base of 2-hydroxy-1-naphthalenecarboxaldehyde

Abstract

The complexes of Schiff base have attracted much attention for their potential biological activities. In this research, five transition metal complexes TM3L2(OAc)2 (TM = Cu, 1; Ni, 2; Co, 3; Mn, 4; Fe, 5) were prepared using a bis-Schiff base of N,N′-bis[(2-hydroxy-1-naphthalenyl)methylene]-propane-1,3-diamine (H2L), which present similar linear trinuclear structures with their three metal ions consolidated by two bis-Schiff base ligands and two acetate ligands. Their antitumor activities in vitro were screened through seven human cancer cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It revealed that complexes 1, 2 and 5 show much higher antitumor activities than the bis-Schiff base ligand and complexes 3 and 4, and even than cisplatin. Among them, complex 1 has the highest inhibitory effects on tumor cells with its IC50 value (half-inhibitory concentration) being less than 0.5 μM for human bladder cancer cell line T-24, at which concentration complex 1 shows nearly no toxicity to the normal cell HL-7702 as revealed by flow cytometry. All of these demonstrate a potential anti-cancer candidate for complex 1, which induces tumor cell apoptosis by blocking T-24 tumor cells at the G2/M phase of the cell cycle, reducing mitochondrial membrane potential, increasing the concentration of reactive oxygen species and Ca2+ in the cell, and changing the expression of proteins.