Synthesis and biological evaluation of a novel artesunate-podophyllotoxin conjugate as anticancer agent

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• 作者：Lei Zhang ; ^{lzhang@zmc.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; ^{lei_chang@yeah.net" class="auth_mail" title="E-mail the corresponding author} ; Fan Chen ; Zeguo Zhang ; Yongzheng Chen ; Jing Wang ; ^{wangjing@zmc.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Artesunate ; Podophyllotoxin ; Cytotoxicity ; Cell cycle ; Microtubule ; Apoptosis
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：26
• 期：1
• 页码：38-42
• 全文大小：1005 K

文摘

A novel conjugate of artesunate–podophyllotoxin was prepared and evaluated for its cytotoxicity against diverse normal and multidrug resistance human cancer cell lines by CCK-8 assay. The conjugate exhibited good cytotoxicity on all the cell lines with IC₅₀ values of 0.453 ± 0.156–3.011 ± 0.272 μM and reduced the resistant factor. The conjugate was further found to disrupt the microtubule network and induce G2/M cell cycle arrest in multidrug resistance K562/ADR cells. Meanwhile, Hoechst staining analysis suggested that conjugate induced cell death by apoptosis. Furthermore, conjugate could downregulate the levels of P-glycoprotein (P-gp) in P-gp overexpressing K562/ADR cells.