scholarly journals Identification of small molecule inhibitor of cyclophilin-A using high throughput virtual screening and molecular docking Studies

2011 ◽  
Author(s):  
Pallapotu Navya ◽  
I Vani Priyadarshini ◽  
Amineni Umamaheswari
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Small Molecule ◽  
High Throughput ◽  
Cyclophilin A ◽  
Small Molecule Inhibitor ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Molecule Inhibitor ◽  
High Throughput Virtual Screening

Inhibition Profiling of Urease and Carbonic Anhydrase II by High- Throughput Screening and Molecular Docking Studies of Structurally Diverse Organic Compounds

2020 ◽  
Vol 17 ◽  
Author(s):  
Majid Ali ◽  
Syed Majid Bukhari ◽  
Asma Zaidi ◽  
Farhan A. Khan ◽  
Umer Rashid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Carbonic Anhydrase ◽  
Metal Complexes ◽  
Organic Compounds ◽  
High Throughput ◽  
High Throughput Screening ◽  
Docking Studies ◽  
Carbonic Anhydrase Ii ◽  
Molecular Docking Studies ◽  
Ic50 Values

Background:: Structurally diverse organic compounds and available drugs were screened against urease and carbonic anhydrase II in a formulation acceptable for high-throughput screening. Objective: The study was conducted to find out potential inhibitors of urease and carbonic anhydrase II. Methods:: Quantification of the possible HITs was carried out by determining their IC50 values. Results and Discussion:: of several screened compounds including derivatives of oxadiazole, coumarins, chromane-2, 4- diones and metal complexes of cysteine-omeprazole showed promising inhibitory activities with IC50 ranging from 47 μM to 412 μM against the urease. The interactions of active compounds with active sites of enzymes were investigated through molecular docking studies which revealed that (R)-1-(4-amino-4-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl) butyl) guanidine possessing IC50 of 47 μM, interacts with one of the nickel metal atom of urease besides further interactions as predictable hydrogen bonds with KCX490, Asp633, His492, His407 and His409 along with Ala440 and 636. Bi-ligand metal complexes of 4-aminoantipyrine based Schiff bases showed activation of urease with AC50 ranging from 68 μM to 112 μM. Almost 21 compounds with varying functional groups including pyrimidines, oxadiazoles, imidazoles, hydrazides and tin based compounds were active carbonic anhydrase II inhibitors presenting 98 μM to 390 μM IC50 values. Several N-substituted sulfonamide derivatives were inactive against carbonic anhydrase II. Conclusion:: Among all the screened compounds, highly active inhibitor of carbonic anhydrase II was (4-(3- hydroxyphenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl) methanone with IC50 of 98.0 μM. This particular compound showed metallic interaction with Zn ion of carbonic anhydrase II through hydroxyl group of phenyl ring.

Molecular Docking and 3D Qsar Studies of C000000956 as a Potent Inhibitor of Bace-1

Drug Research ◽  
2019 ◽  
Vol 69 (08) ◽  
pp. 451-457 ◽  
Author(s):  
Ogunleye Adewale Joseph ◽  
Kikiowo Babatomiwa ◽  
Adelakun Niyi ◽  
Omotuyi Olaposi ◽  
Inyang Olumide
Keyword(s):  
Molecular Docking ◽  
Small Molecule ◽  
3D Qsar ◽  
Small Molecule Inhibitor ◽  
Computational Pipeline ◽  
Qsar Studies ◽  
Neurotoxic Peptide ◽  
Molecule Inhibitor ◽  
Ad Therapy ◽  
Bace 1

Abstract Background BACE-1 is an aspartate protease that is responsible for the proteolysis of amyloid precursor proteins (APP) into beta-amyloid (Aβ), a neurotoxic peptide in patients with Alzheimer’s disease (AD). As such, BACE-1 is a prime pharmacological target in the control of Aβ in the brain and its inhibition will be a sound approach in AD therapy. Methods The computational pipeline which comprised molecular docking (MD), Quantitative Structure Activity Relationship (QSAR) modelling and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies enabled the prediction of molecular interaction and relative inhibitory potentials of the hit compound. Results and Discussion The current study reports a naturally sourced small molecule inhibitor of BACE1 (C000000956) which was obtained through a computational pipeline. Also, pharmacological constraints such as pH dependent activity of the enzyme and blood brain barrier permeation which have been associated with the efficacy of previous BACE-1 inhibitors were well catered for. Our results suggest that orally delivered C000000956 is a potential small molecule inhibitor of BACE-1 which may find usefulness in AD-therapy.

scholarly journals A Novel Dengue Virus Inhibitor, BP13944, Discovered by High-Throughput Screening with Dengue Virus Replicon Cells Selects for Resistance in the Viral NS2B/NS3 Protease

2013 ◽  
Vol 58 (1) ◽  
pp. 110-119 ◽  
Author(s):  
Chi-Chen Yang ◽  
Han-Shu Hu ◽  
Ren-Huang Wu ◽  
Szu-Huei Wu ◽  
Shiow-Ju Lee ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Inhibitor ◽  
Current Treatment ◽  
Stable Cell Line ◽  
Epidemic Disease ◽  
Molecule Inhibitor ◽  
Ns3 Protease

ABSTRACTDengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment is only supportive. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified a potential small-molecule inhibitor, BP13944, via high-throughput screening (HTS) of 60,000 compounds using a stable cell line harboring an efficient luciferase replicon of DENV serotype 2 (DENV-2). BP13944 reduced the expression of the DENV replicon reporter in cells, showing a 50% effective concentration (EC50) of 1.03 ± 0.09 μM. Without detectable cytotoxicity, the compound inhibited replication or viral RNA synthesis in all four serotypes of DENV but not in Japanese encephalitis virus (JEV). Sequencing analyses of several individual clones derived from BP13944-resistant RNAs purified from cells harboring the DENV-2 replicon revealed a consensus amino acid substitution (E66G) in the region of the NS3 protease domain. Introduction of E66G into the DENV replicon, an infectious DENV cDNA clone, and recombinant NS2B/NS3 protease constructs conferred 15.2-, 17.2-, and 3.1-fold resistance to BP13944, respectively. Our results identify an effective small-molecule inhibitor, BP13944, which likely targets the DENV NS3 protease. BP13944 could be considered part of a more effective treatment regime for inhibiting DENV in the future.

scholarly journals High-Throughput Screening Reveals a Small-Molecule Inhibitor of the Renal Outer Medullary Potassium Channel and Kir7.1

2009 ◽  
Vol 76 (5) ◽  
pp. 1094-1103 ◽  
Author(s):  
L. Michelle Lewis ◽  
Gautam Bhave ◽  
Brian A. Chauder ◽  
Sreedatta Banerjee ◽  
Katharina A. Lornsen ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor
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