Four Ni(II), Co(III), Cd(II) complexes based on 5-(pyrazol-1-yl)nicotinic acid: synthesis, X-ray single crystal structure, in vitro cytotoxicity, apoptosis and molecular docking studies

Abstract

We have developed complexes [Ni2(L)2(H2O)4]n (1), [Co2(L)2(H2O)4]n (2), [Cd2(L)2(H2O)2Cl2]n (3) and [Cd2(L)2(H2O)2]n (4), where HL = 5-(pyrazol-1-yl) nicotinic acid. All complexes were characterized by elemental analysis, IR spectroscopy and single crystal X-ray diffraction, showing monoclinic crystal lattice with space group P21/c (1), P21/c (2), P21/c (3), and triclinic crystal lattice with space group P-1 (4), separately. In vitro antitumor screening (MTT method) revealed that 3 exhibited better inhibitory activities than the commercial anticancer drug cisplatin against HeLa tumor cell lines, with IC50 values 9 ± 2. The bindings of these complexes with Fish Sperm DNA were measured by electronic absorption spectra and fluorescence spectroscopy, showing Ksq 0.1867 (1), 0.1589 (2), 0.2332 (3), and 0.1411 (4), with the binding affinities ranked 3 > 1 > 2 > 4. The experimental result showed that these complexes could bind DNA via intercalation. The ability of 1–4 to cleave the pBR322 plasmid DNA was demonstrated by gel electrophoresis assay. The experiment verified that these complexes could induce DNA damage. In addition, flow cytometric analysis showed that 1–4 induced apoptosis of HeLa tumor cell lines; as time increases, the apoptotic impact becomes increasingly significant. The potential of 1–4 as anticancer agents were examined using molecular docking of the complexes with DNA.