Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies
Journal
Journal of medicinal chemistry
Journal Volume
55
Journal Issue
15
Pages
6751
Date Issued
2012-08-09
Author(s)
Yang, Xiaoming
Shi, Qian
Lai, Chin-Yu
Chen, Chi-Yuan
Ohkoshi, Emika
Yang, Shuenn-Chen
Wang, Chih-Ya
Bastow, Kenneth F
Wu, Tian-Shung
Pan, Shiow-Lin
Lee, Kuo-Hsiung
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.
Subjects
PHENANTHROINDOLIZIDINE ALKALOIDS PERGULARININE; PHENANTHROQUINOLIZIDINE ALKALOIDS; THYMIDYLATE SYNTHASE; BIOLOGICAL-ACTIVITY; ANTICANCER AGENTS; CELL-GROWTH; TYLOPHORINIDINE; INHIBITION; PROTEIN; TYLOCREBRINE
SDGs
Publisher
AMER CHEMICAL SOC
Type
journal article