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.