Molecular docking studies of 1-(substituted phenyl)-3-(naphtha [1, 2-d] thiazol-2-yl) urea/thiourea derivatives with human adenosine A2A receptor

Abstract

Computational assessment of the binding interactions of drugs is an important component of computer-aided drug design paradigms. In this perspective, a set of 30 1-(substituted phenyl)-3-(naphtha[1, 2-d] thiazol-2-yl) urea/thiourea derivatives showing antiparkinsonian activity were docked into inhibitor binding cavity of human adenosine A2A receptor (AA2AR) to understand their mode of binding interactions in silico. Lamarckian genetic algorithm methodology was employed for docking simulations using AutoDock 4.2 program. The results signify that the molecular docking approach is reliable and produces a good correlation coefficient (r2 = 0.483) between docking score and antiparkinsonian activity (in terms of % reduction in catalepsy score). Potent antiparkinsonian agents carried methoxy group in the phenyl ring, exhibited both hydrophilic and lipophilic interactions with lower energy of binding at the AA2AR. These molecular docking analyses should, in our view, contribute for further development of selective AA2AR antagonists for the treatment of Parkinson's disease.

Docking studies: <i>In silico</i> aldose reductase inhibitory activity of commercially available flavonoids

“…In the docking studies, if a compound shows lesser binding energy compared to the standard it proves that the compound has higher activity. Analysis of the receptor/ligand complex models generated after successful docking of the flavonoids was based on the parameters such as hydrogen bond interactions, ï -ï interactions, binding energy, RMSD of active site residues and orientation of the docked compound within the active site (Azam et al, 2011). As a general rule, in most of the potent anti inflammatory compounds, both hydrogen bond and ï -ï hydrophobic interactions between the compound and the active sites of the receptor have been found to be responsible for mediating the biological activity.…”

In-silico investigation of the structural requirements for the AMPA receptor antagonism by quinoxaline derivatives

“…To evaluate the accuracy of AutoDock 4.2 as an appropriate docking tool for the present purpose, the co crystallized ligand (ZK200775) were redocked within the inhibitor binding cavity (IBC) of AMPA receptor, and the docked position was compared to the crystal structure position by calculating RMSD value. According to the method of validation, if the RMSD of the best docked conformation is ≤2.0 Å from the experimental one, the used scoring function can be considered as successful [22– 24]. The RMSD values of the native co-crystallized ligand after docking was 0.428 Å, which confirms the reliability of AutoDock for docking compounds under study (Figure 1).…”

Oxasetin fromLophiostomasp. of the Baltic Sea: Identification,in silicoBinding Mode Prediction and Antibacterial Evaluation against Fish Pathogenic Bacteria

“…The docking protocol used in the present study was therefore validated by docking all native co-crystallized ligand molecules to their respective proteins (PDB code: 1JXA, 1YXD, 1JIJ, 1HNJ, 4UAG and 3U2K). According to the method of validation, if the RMSD (root mean square deviation) of the best docked conformation is ≤2.0 Å from the experimental one, the used scoring function is successful [16][17][18]. The RMSD values of the native cocrystallized ligands after docking were ≤2.0 Å (data not shown), which confirms the reliability of AutoDock for docking compound 3 into crystal structures of different antibacterial drug targets.…”