A family of zinc compounds of an anthracene-appended new multifunctional organic scaffold as potent chemotherapeutics against cervical cancer†

Abstract

A family of biologically active novel zinc(II) compounds, namely [Zn(ahpa)(Cl)(H₂O)] (1), [Zn(ahpa)(NO₃)(H₂O)] (2) and [Zn(ahpa)(H₂O)₂](ClO₄) (3), of an anthracene-appended multifunctional organic scaffold, Hahpa (Hahpa = 3-((anthracene-10-ylmethyl)(2-hydroxyethyl)amino)propanoic acid), were synthesized and characterized. Synthesis of 1–3 was accomplished by reacting Hahpa with zinc(II) precursors such as ZnCl₂, Zn(NO₃)₂·6H₂O and Zn(ClO₄)₂·6H₂O, respectively, in the presence of NaOH at room temperature. Compounds 1–3 were characterized by elemental analysis, FTIR, electronic absorption and emission spectroscopy, molar conductivity analysis, and TGA studies. Elemental analysis, molar conductivity analysis, and UV-vis and fluorescence titration results unambiguously confirm the integrity of the compound frameworks. Moreover, the structures of 1–3 were ascertained by density functional theory (DFT) computation using the B3LYP/6-311G level of theory, indicating a distorted square pyramidal geometry around the zinc centers. Furthermore, the anticancer properties of 1–3 were assessed in human cervical cancer (HeLa) cell lines, revealing a significantly high cytotoxicity with IC₅₀ values ranging from 1.09 to 2.11 μM. They showed high selectivity between the normal and cancer cells despite this potency. The anticancer activity of 1–3 was possibly due to an increase in cellular reactive oxygen species (ROS), destruction of cell membrane integrity, and DNA damage occurring via nuclear condensation. Electronic absorption spectroscopy, ethidium bromide (EB) displacement assay and circular dichroism (CD) spectroscopy confirmed the binding affinity and binding mode of 1–3 with DNA in a dose-dependent manner. All three compounds were also able to modulate the expression of p53 tumour suppressor protein and exhibited antitumorigenic activity, whereas their activity remained unaltered in the normal cell. When a comparative assessment of anticancer properties of 1–3 was made, 1 showed a higher cytotoxicity towards the cancer cells in comparison to 2 and 3.