Design, synthesis and biological evaluation of 7-(aryl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline derivatives as potential Hsp90 inhibitors and anticancer agents

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• 作者：Sina Omid Malayeri^a ; ^b ; Khalil Abnous^c ; Atefeh Arab^d ; Maryam Akaberi^e ; Soghra Mehri^c ; Afshin Zarghi^f ; Razieh Ghodsi^a ; ^b ; ^{ghodsir@mums.ac.ir}
• 关键词：Quinolines ; Heat Shock Protein 90 ; Anti-cancer activity ; Her2 ; Molecular docking ; Hsp90 inhibitor
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：25
• 期：3
• 页码：1294-1302
• 全文大小：1467 K
• 卷排序：25

文摘

A new series of quinoline analogues was designed and synthesized as Hsp90 inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against three human cancer cell lines including MCF-7 (human breast cancer cells), DU145 (human prostate cancer cell lines), and A549 (adenocarcinomic human alveolar basal epithelial cells). Some of our compounds (13a-13f) showed significant cytotoxic activity on MCF-7 cells. The most potent anti-proliferative compounds were also tested against Her2, a client protein of Hsp90. Compound 13d that demonstrated the highest antiproliferative activity in the series, was found the most potent one for both Her2 protein degradation and Hsp70 protein induction as well. Molecular modeling studies displayed possible mode of interaction between this compound and N-terminal ATP-binding site of Hsp90.