Target identification of a novel unsymmetrical 1,3,4‐oxadiazole derivative with antiproliferative properties
| Autor: | Sanna L, Zeng Tiansheng, David J. Kelvin, Valentina Bordoni, Luigi Bagella, Lyu Weidong, Li Chengxun, Gérard Aimé Pinna, Gabriele Murineddu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry Gene regulatory network RNA-Seq Computational biology 03 medical and health sciences 0302 clinical medicine Humans Gene Regulatory Networks Protein Interaction Maps KEGG Cell Proliferation Oxadiazoles Binding Sites biology Chemistry Gene Expression Profiling Cell Cycle Reproducibility of Results Cell Biology Cell cycle Small molecule Molecular Docking Simulation Gene Ontology 030104 developmental biology Tubulin Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein Signal transduction Function (biology) HeLa Cells |
| Zdroj: | Journal of Cellular Physiology. 236:3789-3799 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.30120 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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