Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 21, 2010, Pages 6195-6198

  Choi, Hwanho ^a   Lee, Youngseop ^b   Park, Hwangseo ^a   Oh, Dal Seok ^b  

^a Sejong University   (South Korea)

^b Korea Institute of Oriental Medicine (KIOM)   (South Korea)

Author keywords

Anti asthmatic drug; Docking; TNF ; Virtual screening

Indexed keywords

ANTIASTHMATIC AGENT; BAICALEIN; DIMER; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR;

ALLERGIC ASTHMA; ARTICLE; BINDING SITE; COMPETITIVE INHIBITION; COMPUTER AIDED DESIGN; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG BINDING SITE; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; HUMAN; HUMAN CELL; HYDROGEN BOND; IN VITRO STUDY; MOLECULAR DOCKING; PHYSICAL CHEMISTRY; PROTEIN TARGETING; VIRTUAL REALITY; X RAY CRYSTALLOGRAPHY;

ALGORITHMS; ANTI-ASTHMATIC AGENTS; BINDING SITES; COMPUTER SIMULATION; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; MODELS, MOLECULAR; PROTEIN BINDING; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA;

EID: 77957874184     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.08.116     Document Type: Article

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27. 2. The cells were then exposed to lipopolysaccharide (LPS) solution (1 μg/mL) to activate TNF-α receptors and thereby to produce the cell types for allergic asthma. After 14 h from the addition of LPS, the compounds selected from the virtual screening were added to each well and incubated for 2 h to check their inhibitory activities against TNF-α. After staining of the cells with anti-CD 120a antibody and PE-conjugated streptavidin for 1.5 h at 4 °C in the dark, the inhibition of the activity of TNF-α was analyzed with fluorescence activated cell sorting (FACS) techniques. Such a FACS analysis can be useful in this study because the higher is the activity of TNF-α in the cells, the higher should be the fluorescence intensity of the cells. Mean fluorescence intensity of the cells was thus determined on FACScan with the Cell Quest program to estimate the inhibitory activities of the selected compounds. One-way analysis of variance was used to test the statistical significance between groups. P-Values lower than 0.05 were considered statistically significant. The spss program of version 13.0 was used for these statistical analyzes. In this in vitro immunoassay, the known TNF-α inhibitor baicalein was used as the reference.