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 A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating hedgehog pathway-driven tumorigenesis.
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Yang, X., Shi, Q., Lai, C. Y., Chen, C. Y., Ohkoshi, E., Yang, S. C., Wang, C. Y., Bastow, K. F., Wu, T. S., Pan, S. L., Teng, C. M., Yang, P. C., & Lee, K. H. (2012). Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: Design, synthesis, and mechanistic studies. Journal of Medicinal Chemistry, 55(15), 6751-6761. https://doi.org/10.1021/jm3001218