Synthesis and evaluation of biological activities of vibsanin A analogs

Bioorg Med Chem Lett. 2017 Oct 1;27(19):4536-4539. doi: 10.1016/j.bmcl.2017.08.059. Epub 2017 Aug 31.

Abstract

Vibsanin A is an 11-membered vibsane diterpenoid and is reported to induce myeloid cell differentiation via activation of protein kinase C (PKC) without tumor-promoting activity. Therefore, vibsanin A is thought to be an attractive compound for acute myeloid leukemia (AML) therapy. In this study, we synthesized vibsanin A analogs and compared the activity of these compounds for PKC activation and myeloid cell differentiation. We found that the hydroxymethyl group in vibsanin A is an important substituent to induce differentiation of AML cells. Collectively, our results showed the biochemical features of vibsanin A and provided new insights into the development of new antileukemic drugs.

Keywords: Acute myeloid leukemia; Differentiation; Protein kinase C; Vibsanin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Myeloid Cells / drug effects*
  • Myeloid Cells / pathology
  • Protein Kinase C / metabolism*
  • Structure-Activity Relationship

Substances

  • Diterpenes
  • vibsanin A
  • Protein Kinase C