Metal complexes containing vitamin B6-based scaffold as potential DNA/BSA-binding agents inducing apoptosis in hepatocarcinoma (HepG2) cells

Abstract

A ligand (HL) was synthesized from the pyridoxal hydrochloride (vitamin B6 form) and 1-(2-Aminoethyl)piperidine in one single step. The metal complexes [Zn(L)(Bpy)]NO₃ (1), [Cu(L)(Bpy)]NO₃ (2), and [Co(L)(Bpy)]NO₃ (3) were prepared by tethering HL and 2,2′-bipyridine. The synthesized HL and metal complexes 1–3 were thoroughly characterized using spectroscopic techniques such as ¹H NMR, ¹³C NMR, FTIR, EI-MS, molar conductance, and magnetic moment, in addition to CHN elemental analysis. The geometry of complexes was square pyramidal around the metal ions {Zn(II), Cu(II), and Co(II)}. The interaction of ligand and metal complexes with DNA and BSA macromolecules was accomplished by UV–Vis absorption and fluorescence spectroscopy in vitro. The hyperchromism in band at 303–325 with no shift supports the groove binding with some partial intercalation in grooves. Similarly, in BSA-binding studies, complex 2 shows greater binding potential in the hydrophobic core probably near the Trp-212 in the subdomain IIA. Furthermore, complex 2 shows excellent cytotoxicity on HepG2 cancer cells with IC₅₀ = 25.0 ± 0.45 µM. The detailed analysis by cell-cycle studies shows cell arrest at the G2/M phase. The type of cell death was authenticated by an annexin V-FTIC dual staining experiment that reveals maximum death by apoptosis together with non-specific necrosis.