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Target identification of a novel unsymmetrical 1,3,4‐oxadiazole derivative with antiproliferative properties
Author(s) -
Weidong Lyu,
Sanna Luca,
Bordoni Valentina,
Tiansheng Zeng,
Chengxun Li,
Murineddu Gabriele,
Pinna Gerard A.,
Kelvin David J.,
Bagella Luigi
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30120
Subject(s) - kegg , gene , computational biology , biology , tubulin , function (biology) , chemistry , gene ontology , genetics , gene expression , microtubule
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.