Discovery of 4-benzoylamino-N-(prop-2-yn-1-yl)benzamides as novel microRNA-21 inhibitors

Bioorganic & Medicinal Chemistry
Cong-shan JiangShe-Min Lu

Abstract

MicroRNA-21, as an oncogenic miRNA, has caught great attention for medicinal chemists to develop its novel inhibitors for cancer therapy. In the present study, we designed 4-benzoylamino-N-(prop-2-yn-1-yl)benzamides as miR-21 inhibitor candidates on the basis of scaffold hopping. Eighteen compounds were synthesized. The inhibitory activities of synthesized compounds against the expression of miR-21 were evaluated using stem loop RT-qPCR and compound 1j was discovered as the most potent compound, which displayed a time and concentration dependent inhibition manner. In addition, various functional assays such as the expression of miR-21 target gene detected by Western blotting and the cell growth and apoptosis detected by flow cytometric analysis were checked in Hela (human epithelioid cervix carcinoma) and U-87 MG (human glioblastoma) cells to confirm its activity. The results indicate that compound 1j can enhance apoptosis, retard proliferation, and up-regulate PDCD4, a target protein of miR-21. In addition, the compound 1j does not influence the expression of multiple miRNAs and the genes that participate in miRNA universal biosynthesis pathway. These results strongly support the assumption that title compounds can serve as a ...Continue Reading

Citations

Apr 26, 2019·Biotechnology and Applied Biochemistry·Yuan-Yuan HeiSan-Qi Zhang
Jul 11, 2020·Beilstein Journal of Organic Chemistry·Katarzyna JustynaKatarzyna M Błażewska
Sep 28, 2017·Cell Biology International·Rafael P de CamposMárcia R Wink
Dec 26, 2018·European Journal of Medicinal Chemistry·Guilherme Felipe Dos Santos FernandesJean Leandro Dos Santos
Mar 7, 2021·International Journal of Molecular Sciences·Rebecca RaueBernhard Brüne
Jun 2, 2021·Journal of Medicinal Chemistry·Farzad Zamani, Takayoshi Suzuki
Jun 13, 2021·Current Opinion in Chemical Biology·Jared T BaisdenMatthew D Disney
May 18, 2019·ACS Medicinal Chemistry Letters·Amanda L GarnerArya Menon

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