Molecular docking analysis and spectroscopic investigations of zinc(II), nickel(II) N-phthaloyl-β-alanine complexes for DNA binding: Evaluation of antibacterial and antitumor activities

Herein, computational molecular docking, UV/visible and fluorescence spectroscopic techniques have been used to explore the DNA binding interactions of N-phthaloyl-b-alanine (NPA) ligand and its Zn(II) and Ni(II) complexes (NPAZn, NPANi). The compounds were further tested for anti-bacterial and anti-tumor activities. Docking analysis depicted that ligand NPA interacted with DNA via intercalation, while its metal complexes showed mixed mode of interactions. Spectroscopic experiments for DNA binding studies were run under physiological conditions of pH (stomach; 4.7, blood; 7.4) and temperature (37 degrees C). Based on changes in spectral responses, binding parameters for all the compounds were obtained which showed comparatively greater binding constant values (K-b: UV; 1.16 x 10(5) M-1, Flu; 1.35 x 10(5) M-1) and more negative free energy changes (Delta G: UV; -30.00 kJ mol(-1), Flu; -30.44 kJ mol(-1)) for NPAZn at pH 4.7. The overall, binding results were also found more significant at stomach pH. Dynamic K-D and bimolecular K-B constants were evaluated, and the values affirmed the participation of static process for each compound-DNA binding. The greater binding site size values (n > 1) of metal complexes NPAZn and NPANi indicated other sites availability of intercalative compounds. DNA viscosity variation by increasing compound's concentration further verified the compound-DNA interaction. Antibacterial and tumor inhibitory activities were observed significant for both metal complexes, while ligand has shown no activity. The greater binding affinity of metal complexes, as evaluated both computationally and spectroscopically, further validated the lower IC50 values of complexes as compared to ligand. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

In this study, computational molecular docking and spectroscopic techniques were used to investigate the DNA binding interactions of NPA ligand and its metal complexes. The metal complexes exhibited stronger binding affinity and significant antibacterial and tumor inhibitory activities compared to the ligand.