Target identification of a novel unsymmetrical 1,3,4-oxadiazole derivative with antiproliferative properties

Lyu Weidong; Luca Sanna; Valentina Bordoni; Zeng Tiansheng; Li Chengxun; Gabriele Murineddu; Gerard A. Pinna; David J. Kelvin; Luigi Bagella

doi:10.1002/jcp.30120

Target identification of a novel unsymmetrical 1,3,4-oxadiazole derivative with antiproliferative properties

Lyu Weidong, Luca Sanna, Valentina Bordoni, Zeng Tiansheng, Li Chengxun, Gabriele Murineddu, Gerard A. Pinna, David J. Kelvin, Luigi Bagella

Medicine

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

1,3,4-Oxadiazole derivatives are widely used in research on antineoplastic drugs. Recently, we discovered a novel unsymmetrical 1,3,4-oxadiazole compound with antiproliferative properties called 2j. To further investigate its possible targets and molecular mechanisms, RNA-seq was performed and the differentially expressed genes (DEGs) were obtained after treatment. Data were analyzed using functional (Gene Ontology term) and pathway (Kyoto Encyclopedia of Genes and Genomes) enrichment of the DEGs. The hub genes were determined by the analysis of protein-protein interaction networks. The connectivity map (CMap) information provided insight into the model action of antitumor small molecule drugs. Hub genes have been identified through function gene networks using STRING analysis. The small molecular targets obtained by CMap comparison showed that 2j is a tubulin inhibitor and it acts mainly affecting tumor cells through the cell cycle, FoxO signaling pathway, apoptotic, and p53 signaling pathways. The possible targets of 2j could be TUBA1A and TUBA4A. Molecular docking results indicated that 2j interacts at the colchicine-binding site on tubulin.

Original language	English
Pages (from-to)	3789-3799
Number of pages	11
Journal	Journal of Cellular Physiology
Volume	236
Issue number	5
DOIs	https://doi.org/10.1002/jcp.30120
Publication status	Published - May 2021

Bibliographical note

Funding Information:
Funding support was provided by “Fondo di Ateneo per la Ricerca 2019,” University of Sassari (Luigi Bagella), by Li Ka‐Shing Foundation, International Institute of Infection and Immunity, Shantou University Medical College, and Dalhousie Medical Research Foundation (David J. Kelvin). David J. Kelvin is the recipient of the Tier I Canada Research Chair in Translational Vaccinology and Inflammation. Valentina Bordoni is financially supported by the PhD School in Life Sciences and Biotechnologies at the University of Sassari (P.O.R. F.S.E. 2014‐2020).

Publisher Copyright:
© 2020 Wiley Periodicals LLC

ASJC Scopus Subject Areas

Physiology
Clinical Biochemistry
Cell Biology

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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@article{6be82cda22f94d19b8411665c358f037,

title = "Target identification of a novel unsymmetrical 1,3,4-oxadiazole derivative with antiproliferative properties",

abstract = "1,3,4-Oxadiazole derivatives are widely used in research on antineoplastic drugs. Recently, we discovered a novel unsymmetrical 1,3,4-oxadiazole compound with antiproliferative properties called 2j. To further investigate its possible targets and molecular mechanisms, RNA-seq was performed and the differentially expressed genes (DEGs) were obtained after treatment. Data were analyzed using functional (Gene Ontology term) and pathway (Kyoto Encyclopedia of Genes and Genomes) enrichment of the DEGs. The hub genes were determined by the analysis of protein-protein interaction networks. The connectivity map (CMap) information provided insight into the model action of antitumor small molecule drugs. Hub genes have been identified through function gene networks using STRING analysis. The small molecular targets obtained by CMap comparison showed that 2j is a tubulin inhibitor and it acts mainly affecting tumor cells through the cell cycle, FoxO signaling pathway, apoptotic, and p53 signaling pathways. The possible targets of 2j could be TUBA1A and TUBA4A. Molecular docking results indicated that 2j interacts at the colchicine-binding site on tubulin.",

author = "Lyu Weidong and Luca Sanna and Valentina Bordoni and Zeng Tiansheng and Li Chengxun and Gabriele Murineddu and Pinna, {Gerard A.} and Kelvin, {David J.} and Luigi Bagella",

note = "Funding Information: Funding support was provided by “Fondo di Ateneo per la Ricerca 2019,” University of Sassari (Luigi Bagella), by Li Ka‐Shing Foundation, International Institute of Infection and Immunity, Shantou University Medical College, and Dalhousie Medical Research Foundation (David J. Kelvin). David J. Kelvin is the recipient of the Tier I Canada Research Chair in Translational Vaccinology and Inflammation. Valentina Bordoni is financially supported by the PhD School in Life Sciences and Biotechnologies at the University of Sassari (P.O.R. F.S.E. 2014‐2020). Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC",

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AU - Weidong, Lyu

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AU - Tiansheng, Zeng

AU - Chengxun, Li

AU - Murineddu, Gabriele

AU - Pinna, Gerard A.

AU - Kelvin, David J.

AU - Bagella, Luigi

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PY - 2021/5

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Target identification of a novel unsymmetrical 1,3,4-oxadiazole derivative with antiproliferative properties

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

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