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

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.

Automated summary

A novel unsymmetrical 1,3,4-oxadiazole compound called 2j was discovered with antiproliferative properties, which acts as a tubulin inhibitor mainly affecting tumor cells through the cell cycle, FoxO signaling pathway, apoptotic, and p53 signaling pathways. The possible targets of 2j were identified as TUBA1A and TUBA4A, and molecular docking results showed its interaction at the colchicine-binding site on tubulin. Through RNA-seq and functional enrichment analysis, the molecular mechanisms and potential targets of 2j were further investigated.