Title:In vitro Synthesis, Structure Elucidation, and Antioxidant Properties of Platinum(IV)-hydrazide Complexes: Molecular Modeling of Free- Hydrazides Suggested as Potent Lipoxygenase Inhibitor
Volume: 18
Issue: 1
Author(s): Rooma Badar, Uzma Ashiq *, Rifat Ara Jamal, Parveen Akhter, Mohammad Mahroof-Tahir, Sana Gul and Syed Tahir Ali
Affiliation:
- Department of Chemistry, University of Karachi, Karachi-75270,Pakistan
Keywords:
DPPH radical, superoxide, nitric oxide, lipoxygenase, platinum(IV), hydrazide, in silico docking.
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.