Current Issue : October-December Volume : 2012 Issue Number : 4 Articles : 7 Articles
The objective of the current study is to evaluate the lipoxygenase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like Biochanin, Isorhamnetin, Tricetin, Tricin, and Okanin were selected. Azelastine, a known lipoxygenase inhibitor was used as the standard. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Three important parameters like binding energy, inhibition constant and intermolecular energy were determined. The results showed that all the selected flavonoids showed lesser binding energy ranging between -3.77 kcal/mol to -3.07 kcal/mol when compared with that of the standard (-3.72 kcal/mol). Intermolecular energy (-4.96 kcal/mol to -4.86 kcal/mol) and inhibition constant (1.73 mM to 5.64 mM) of the ligands also coincide with the binding energy. All the selected flavonoids consist of benzopyran ring in its basic nucleus, which would have contributed to its lipoxygenase inhibitory activity. These molecular docking analyses could lead to the further development of potent lipoxygenase inhibitors for the treatment of inflammation....
Several cholinesterase inhibitors are either being utilized for symptomatic treatment of Alzheimer's disease or are in advanced clinical trials. E2020, marketed as Aricept, is a member of a large family of N-benzylpiperidine-based acetylcholinesterase (AChE) inhibitors developed, synthesized and evaluated by the Eisai Company in Japan. Based on these observations we have tried to discover novel acetylcholinesterase inhibitor using target search option in zinc database. Structure of target molecule zinc_634140 was obtained and docked against acetylcholinesterase (pdb id- 1eve) enzyme using Autodock 4.2. The docking studies divulge that compound zinc_634140 interact with receptor through hydrogen bonding with polar, acidic amino acid residues and showed close proximity towards greasy surface of receptor. The docking analysis suggest that compound zinc_634140 and E2020 (Aricept) showed nearly identical binding with acetylcholinesterase receptor. Further docking of compound zinc_634140 involved four water molecule while docking results of E2020 (Aricept) displayed involvement of two water molecule. Further optimization of compound zinc_634140 suggests addition of piperidine ring for future structural optimization to enhance arene-arene and arene-cation interactions with acetylcholinesterase receptor....
Several studies have linked Quinone Reductase 2 to the generation of quinone free radicals, several neuronal degenerative diseases, and cancer. There is no definitive correlation between traditionally obtained MT3 ligand affinity and hQR2 inhibition exists limiting the understanding of how these ligands are accommodated in the hQR2 active site. Based on these outlooks we have tried to identify novel target using target search option in zinc database to explore probable reason for affinity and inhibition of Quinone Reductase 2 using docking studies. The docking analysis divulge that compound zinc_6182368 inhibit quinone reductase 2 via hydrogen bonding, arene-arene interaction by acquiring different enantiomeric forms in the active site of receptor. The analysis divulge that compound zinc_6182368 bind to the quinone reductase in a stereoselective manner, existence of chiral centre is essential to acquire bioactive conformation within the active site while arene-arene interaction may enhance binding affinity of ligand towards receptor surface....
Researchers have recently focused on selective COX-2 inhibitors, which are believed to reduce inflammation without influencing normal physiologic functions by inhibiting only COX-2. In this background we have endeavour to identify new scaffold from zinc database as selective cyclooxygenase 2 inhibitor. The docking analysis revealed that sulfone oxygen of sulphonamide cluster apparantly involved in hydrogen bonding with residues namely His 90, Arg513 while amine site in sulphonamide form hydrogen bond with Leu352 thereby inhibiting the cox 2 in a selective manner. The present analysis is valuable for the future design of novel cox 2 inhibitor....
Caspase-6 is a cysteine protease implicated in neuronal survival and apoptosis. Deregulation of caspase-6 activity was linked to several neurodegenerative disorders including Alzheimer's and Huntington's Diseases. In an attempt to recognize novel agents to cure Alzheimer's and Huntington's Diseases, we have identified a lead molecule based on target search option in zinc database. The lead compound zinc_12378847 inhibit caspase-6 cystein proteases at 1µm (Ki 1 µm). The present docking analyses conclude that compound zinc_12378847 was recognized as novel lead for targeting caspase-6 enzyme. It inhibits target protein by hydrogen bonding, arene-arene and nonbonding interactions. The proposed analysis may be useful for the future design and optimization of novel caspase-6 target....
Cathepsin L-like proteinases (CAL) are major digestive proteinases in the beetle Tenebrio molitor. Procathepsin Ls 2 (pCAL2) and 3 (pCAL3) were expressed as recombinant proteins in Escherichia coli. With the aim to find new agent against Cathepsin L-like proteinases, we have carried out target search in the zinc database and identified a target compound (zinc_200316000) using in silico docking analysis. Structure of the target protein was retrieved from protein data bank (pdb i.d.3qj3) and in silico analysis was performed on Autodock 4.2. The docking analysis revealed that ligand zinc_200316000 interacts with target protein via arene-cation and nonbonding interactions. The analysis divulges that present in silico docking results may be helpful for the optimization of the ligand for enhanced biological activity and future drug design....
Phosphodiesterases (PDEs) comprise a family of enzymes that modulate the immune response, inflammation, and memory, among many other functions. There are three types of PDEs: cAMP-specific, cGMP-specific, and dual-specific. In order to identify novel lead effective at micromole concentration, we have carried out target search option I zinc database and recognized a lead (zinc_197999526) effective at 1µm (Ki 1 µm). The docking analysis revealed that lead molecule interact with phosphodiesterases enzyme through arene-cation, hydrogen bonding and nonbonding interactions. The present analysis proposes a novel compound zinc_197999526 effective at micromole level and inhibit phosphodiesterases throgh hydrogen bonding and arene-cation interactions. The present analysis may be useful for future drug design....
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