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Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies.

ABSTRACT: Various E-ring hydroxylated antofine and cryptopleurine analogues were designed, synthesized, and tested against five human cancer cell lines. Interesting structure-activity 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 ?-catenin in A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating hedgehog pathway-driven tumorigenesis.

SUBMITTER: Yang X

PROVIDER: S-EPMC3422873 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies.

Yang Xiaoming X Shi Qian Q Lai Chin-Yu CY Chen Chi-Yuan CY Ohkoshi Emika E Yang Shuenn-Chen SC Wang Chih-Ya CY Bastow Kenneth F KF Wu Tian-Shung TS Pan Shiow-Lin SL Teng Che-Ming CM Yang Pan-Chyr PC Lee Kuo-Hsiung KH

Journal of medicinal chemistry 20120723 15

Various E-ring hydroxylated antofine and cryptopleurine analogues were designed, synthesized, and tested against five human cancer cell lines. Interesting structure-activity 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 β-catenin in ...[more]

PMID: 22823514

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