Target identification of small molecules with antiproliferative properties

1,3,4-oxadiazole derivatives are widely used in the research of antineoplastic drugs. On the basis of previous work, 16 new 1,3,4-oxadiazole compounds with different structural types were designed and synthesized on the basis of 2j, in order to obtain new efficacious anticancer with low toxicity and side effects.In the present research, the results showed that 7FB, 16FB, 8VDB, 22VDB, and 23VDB had a significant inhibitory effect on tumor cell lines and caused cell cycle arrest at G2/M phase in a time-dependent manner in Hela and PC-3 cells.In order to further study 2j and its derivatives possible targets and identify molecular mechanisms, the DEGs were determined after 2j, 16FB and 8VDB treatment. RNA-seq was performed and data were analyzed using functional (GO term) and pathway (KEGG) enrichment of the differentially expressed genes (DEGs). The hub genes of anti-tumor small molecules were determined by the analysis of protein-protein interaction networks. The results showed that 2j and its derivatives were tubulin inhibitors, mainly affected tumor cells through the cell cycle, FoxO signaling pathway, and apoptotic and p53 signaling pathways. Based on STRING analysis of function gene networks, hub genes were identified and the small molecular targets obtained by CMap comparison, the possible targets of 2j, 16FB and 8VDB could be TUBA1A, TUBA4A, and TUBB. Molecular docking results indicated that 2j interacted at the colchicine-binding site on tubulin.