期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 55, 期 15, 页码 6751-6761出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm3001218
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资金
- National Cancer Institute [CA 17625]
- National Research Program for Genomic Medicine [DOH98-TD-G-111-007]
- Cancer Research Center of Excellence (CRC) [DOH-100-TD-C-111-005]
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 beta-catenin in A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating hedgehog pathway-driven tumorigenesis.
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