In vitro Synthesis, Structure Elucidation, and Antioxidant Properties of Platinum(IV)-hydrazide Complexes: Molecular Modeling of Free- Hydrazides Suggested as Potent Lipoxygenase Inhibitor

Abstract

Background: A combination of biologically active ligand and metal in one molecule may increase the activity and reduce the toxicity. Objectives: In this study, the synthesis and characterization of platinum(IV) complexes with bioactive hydrazide ligands are discussed. Method: Elemental analysis, conductivity measurements, and spectroscopic studies were used to elucidate the structure of complexes. Results: Our study suggests that hydrazide ligands coordinate with Pt(IV) in a bidentate fashion. The platinum(IV) complexes have octahedral geometry with a metal to ligand ratio of 1:2. Hydrazide ligands were coordinated with central metal platinum(IV) by oxygen of carbonyl group and nitrogen of primary amine. Synthesized complexes exhibited variable DPPH radical scavenging and lipoxygenase inhibition activity. Furthermore, it is also found that Pt(IV)-hydrazide complexes are more potent superoxide and nitric oxide radical scavengers than their uncoordinated hydrazide ligands, while in the case of lipoxygenase enzyme inhibition, some of the free hydrazide ligands are more active than their respective Pt(IV) complexes. In silico docking technique explores molecular interactions of synthesized ligands in the active site of the lipoxygenase enzyme. Predicted docking energies are in good agreement with experimental data suggesting that in silico studies might be useful for the discovery of therapeutic candidates. Conclusion: Structure-function relationship demonstrates that the radical scavenging and enzyme inhibition activities of the Pt(IV) compounds are affected by the nature of the ligand, position of substituent, electronic and steric effects. However, electronic factors seem to play a more important role than other factors.