2. Academic Validation
  3. Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies

Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies

  • J Med Chem. 2012 Aug 9;55(15):6751-61. doi: 10.1021/jm3001218.
Xiaoming Yang 1,  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
Affiliations

Affiliation

  • 1 Natural Products Research Laboratories and ‡Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599-7568, United States.
PMID: 22823514 DOI: 10.1021/jm3001218
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.

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