Benzohydrazide derivative metal complex's antimicrobial and inhibitory effects on liver cancer cell lines and quinone oxidoreductase 2: experimental, molecular docking, and DFT investigations

The activity of benzohydrazide derivatives has good biological activity against many bacteria species and different cancer cell lines, and the significance of metal complexes in boosting bioavailability and inhibitory action have both been highlighted in recent research. Here we synthesized (E)-N'-(4-(dimethylamino)benzylidene)benzohydrazide (HDmby) and its seven metal (II) complexes, including [MCl2(HDmby)] {where MII = Pd (1), Pt(2), Zn (3), Cd(4), and Hg(5)} and [M(Dmby)2] {where MII = Pd (6), and Hg(7)}, with good yields (71–93%) and characterized by molar conductivities, elemental analysis, FTIR, and NMR (1H and 13C) spectroscopic techniques. This study focuses on the analysis of the HDmby ligand and its metal complexes using theoretical calculations. The results reveal excellent agreement between the calculated and experimental data, highlighting the stability of both the ligand and its metal complexes. The HOMO and LUMO energies indicate their stability, with negative energy values. The prepared complexes displayed respectable activity against S. aureus, B. subtilis, and E. coli. [PtCl2(HDmby)] complex showed the highest inhibition value (DIZ is 20, 23, and 25mm) against all types of bacteria. In other combinations, the free ligand doesn't show outstanding results. Also screened the cytotoxic activity against the human liver cancer cells, and the results indicated that complexes (2) and (3) showed higher cytotoxic activity with IC50 = 8.08 ± 0.736 and 4.03 ± 0.271 µM, respectively. As the high activity of quinone oxidoreductase 2 (NQO2) was correlated to liver cancer incidence, the inhibitory activity of HDmby and its complexes on NQO2 was investigated using a molecular docking approach. HDmby has demonstrated a remarkable capacity to form hydrogen bonds, whereas its zinc complex has demonstrated an enhanced energy binding score that is on par with doxorubicin, which is being studied as a reference inhibitor. The outcomes demonstrated a strong degree of concordance with the experimental data and emphasized the significance of organometallic compounds in cancer chemotherapy.