Three metal complexes with a pyridyl Schiff base: cytotoxicity, migration and mechanism of apoptosis

Abstract

Three metal complexes [CuL(NO₃)]_n (1), [Cd(HL)(NO₃)₂]_n (2) and [EuL(HCOOH)(H₂O)(NO₃)₂] (3) were synthesized with a pyridyl Schiff ligand L (N′-[(1E)-pyridin-2-ylmethylidene]pyridine-4-carbohydrazide). A crystallographic study revealed that complexes 1 and 2 have a chain structure, and complex 3 is a zero-dimensional monomer. In vitro cytotoxicity studies showed that complex 2 had the best antiproliferative activity against SMMC-7721 cells and complex 3 had the best antiproliferative activity against MDA-MB-231 cells with single-digit IC₅₀ values, both exceeding those of the control drug cisplatin by far. The cell invasion and migration ability through the transwell assay and wound-healing assay showed that the selected complexes could inhibit the invasion and migration of cancer cells. The Hoechst staining assay and ROS generation assay with SMMC-7721 cells indicated that the cytotoxic effects of complex 2 involved apoptosis induction through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of complex 2 on SMMC-7721 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G₀/G₁ phase of the cell cycle. In addition, complex 2 showed significant inhibition against B. dysentery with an inhibition circle diameter of 24 mm.