Structure and Activity Analysis of Inauhzin Analogs as Novel Antitumor Compounds That Induce p53 and Inhibit Cell Growth

Qi Zhang, Derong Ding, Shelya X. Zeng, Qi Zhuang Ye, Hua Lu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Identifying effective small molecules that specifically target the p53 pathway in cancer has been an exciting, though challenging, approach for the development of anti-cancer therapy. We recently identified Inauhzin (INZ) as a novel p53 activator, selectively and efficiently suppressing tumor growth without displaying genotoxicity and with little toxicity to normal cells. In order to reveal the structural features essential for anti-cancer activity of this small molecule, we have synthesized a panel of INZ analogs and evaluated their ability to induce cellular p53 and to inhibit cell growth in cell-based assays. This study as described here leads to the discovery of INZ analog 37 that displays much better potency than INZ in both of p53 activation and cell growth inhibition in several human cancer cell lines including H460 and HCT116+/+ cells. This INZ analog exhibited much less effect on p53-null H1299 cells and HCT116-/- cells, and importantly no toxicity on normal human p53-containing WI-38 cells. Hence, our results not only unveil key chemical features for INZ activity, but also identify the newly synthesized INZ analog 37 as a better small molecule for further development of anti-cancer therapy.

Original languageEnglish (US)
Article numbere46294
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 24 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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