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Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database

According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130)(2) and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals D...

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Autores principales: Wang, Jing, Qiao, Chunxia, Xiao, He, Lin, Zhou, Li, Yan, Zhang, Jiyan, Shen, Beifen, Fu, Tinghuan, Feng, Jiannan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170619/
https://www.ncbi.nlm.nih.gov/pubmed/28008232
http://dx.doi.org/10.2147/DDDT.S118457
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author Wang, Jing
Qiao, Chunxia
Xiao, He
Lin, Zhou
Li, Yan
Zhang, Jiyan
Shen, Beifen
Fu, Tinghuan
Feng, Jiannan
author_facet Wang, Jing
Qiao, Chunxia
Xiao, He
Lin, Zhou
Li, Yan
Zhang, Jiyan
Shen, Beifen
Fu, Tinghuan
Feng, Jiannan
author_sort Wang, Jing
collection PubMed
description According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130)(2) and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist.
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spelling pubmed-51706192016-12-22 Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database Wang, Jing Qiao, Chunxia Xiao, He Lin, Zhou Li, Yan Zhang, Jiyan Shen, Beifen Fu, Tinghuan Feng, Jiannan Drug Des Devel Ther Original Research According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130)(2) and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist. Dove Medical Press 2016-12-15 /pmc/articles/PMC5170619/ /pubmed/28008232 http://dx.doi.org/10.2147/DDDT.S118457 Text en © 2016 Wang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Wang, Jing
Qiao, Chunxia
Xiao, He
Lin, Zhou
Li, Yan
Zhang, Jiyan
Shen, Beifen
Fu, Tinghuan
Feng, Jiannan
Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database
title Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database
title_full Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database
title_fullStr Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database
title_full_unstemmed Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database
title_short Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database
title_sort structure-based virtual screening and characterization of a novel il-6 antagonistic compound from synthetic compound database
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5170619/
https://www.ncbi.nlm.nih.gov/pubmed/28008232
http://dx.doi.org/10.2147/DDDT.S118457
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