In Silico Inhibitory Activity against Caspase 3 by Zinc (II) Coordinated Complexes

Abstract

Aims: The presented research paper is aimed to prevalence of apoptosis for the first time by using in silico molecular docking and simulation using caspase-3 zymogen and zinc-coordinated compounds. Antioxidant activities of the coordinated complexes were compared to the positive controls (BHT and ascorbic acid). Study design:  Molecular docking analysis was performed by using Autodock 4.2, setting at 150x140x110 Gridbox, center at -57.616, 31.092, 88.666 with 0.375 Å spacing. Their antioxidant activity was tested by FRAP and DPPH assay. Place and Duration of Study: Department of Chemistry and department of molecular medicine, Faculty of Medicine, University of Malaya laboratories between January 2014 – July 2014 Methodology: Compounds derived from zinc(II) ion give rise to coordination complexes exhibited CHN, NMR (1H & 13C) and FT-IR spectra consistent with the proposed structures. Based on the x-ray crystal structure, one of the derivatives is a mononuclear square-pyramidal metal complex, with τ value of 0.35. The molecular docking simulation formed between compounds and caspase 3 showed the ligands bind to the active-site gorge well positioned in the active-site gorge. Results: The residues that have been involved in this protein-ligand interaction docked well by using Autodock 4.2, setting at 150x140x110 Gridbox, center at -57.616, 31.092, 88.666 with 0.375 Å spacing in the hydrophobic pocket. Their antioxidant activity tested revealed their FRAP assay values of 531.11±0.021 and 1886.11±0.008 higher than value of 187.3±2.6 shown by BHT used as standard. The compounds showed IC50 values 21.50±0.009 and 14.80±0.002 lower than ascorbic acid with an IC50 value of 2.26±0.001 μg/mL. Conclusion: Synthesized zinc(II) complexes have been confirmed to inhibit the activity of caspase 3 both in silico and in vitro and were tested for antioxidant activity by both FRAP and DPPH methods.