Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies.
Yang X, Shi Q, Lai CY, Chen CY, Ohkoshi E, Yang SC, Wang CY, Bastow KF, Wu TS, Pan SL, Teng CM, Yang PC, Lee KH.
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.