Antitumor Agents 295. E-Ring Hydroxylated Antofine and Cryptopleurine Analogues as Antiproliferative Agents: Design, Synthesis, and Mechanistic Studies

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• 作者：Xiaoming Yang ; Qian Shi ; Chin-Yu Lai ; Chi-Yuan Chen ; Emika Ohkoshi ; Shuenn-Chen Yang ; Chih-Ya Wang ; Kenneth F. Bastow ; Tian-Shung Wu ; Shiow-Lin Pan ; Che-Ming Teng ; Pan-Chyr Yang ; Kuo-Hsiung Lee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：August 9, 2012
• 年：2012
• 卷：55
• 期：15
• 页码：6751-6761
• 全文大小：441K
• 年卷期：v.55,no.15(August 9, 2012)
• ISSN：1520-4804

文摘

Various E-ring hydroxylated antofine and cryptopleurine analogues were designed, synthesized, and tested against five human cancer cell lines. Interesting structure鈥揳ctivity relationship (SAR) correlations were found among these new compounds. The most potent compound 13b was further tested against a series of nonsmall cell lung cancer (NSCLC) cell lines in which it showed impressive antiproliferative activity. Mechanistic studies revealed that 13b is able to down-regulate HSP90 and 尾-catenin in A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating hedgehog pathway-driven tumorigenesis.