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 β-catenin in A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating hedgehog pathway-driven tumorigenesis.
Authors	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
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 55 Issue 15 Pg. 6751-61 (Aug 09 2012) ISSN: 1520-4804 [Electronic] United States
PMID	22823514 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	13-hydroxycryptopleurine Alkaloids Antineoplastic Agents HSP90 Heat-Shock Proteins Indoles Phenanthrolines Quinolizidines antofine beta Catenin cryptopleurine
Topics	Adenocarcinoma Alkaloids (chemical synthesis, chemistry, pharmacology) Antineoplastic Agents (chemical synthesis, chemistry, pharmacology) Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Cell Proliferation (drug effects) Down-Regulation Drug Design Drug Screening Assays, Antitumor HSP90 Heat-Shock Proteins (biosynthesis) Humans Indoles (chemical synthesis, chemistry, pharmacology) Lung Neoplasms Phenanthrolines (chemical synthesis, chemistry, pharmacology) Quinolizidines (chemical synthesis, chemistry, pharmacology) Stereoisomerism Structure-Activity Relationship beta Catenin (biosynthesis)

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