Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1

  • J Nat Prod. 2015 Aug 28;78(8):1969-76. doi: 10.1021/acs.jnatprod.5b00324.
Shi-Wei Chao ,  Ming-Yuan Su  1  2 ,  Lih-Chu Chiou ,  Liang-Chieh Chen ,  Chung-I Chang  1  2 ,  Wei-Jan Huang  3  4
Affiliations
  • 1. Institute of Biological Chemistry, Academia Sinica , Taipei 115, Taiwan.
  • 2. Institute of Biochemical Sciences, College of Life Science, National Taiwan University , Taipei 106, Taiwan.
  • 3. Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs , Taipei 110, Taiwan.
  • 4. School of Pharmacy, National Defense Medical Center , Taipei 114, Taiwan.
PMID: 26275107 DOI: 10.1021/acs.jnatprod.5b00324
Abstract

A new method is applied to synthesize hispidulin, a natural flavone with a broad spectrum of biological activities. Hispidulin exhibits inhibitory activity against the oncogenic protein kinase Pim-1. Crystallographic analysis of Pim-1 bound to hispidulin reveals a binding mode distinct from that of quercetin, suggesting that the binding potency of Flavonoids is determined by their hydrogen-bonding interactions with the hinge region of the kinase. Overall, this work may facilitate construction of a library of hispidulin-derived compounds for investigating the structure-activity relationship of flavone-based Pim-1 inhibitors.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-N1950
    Hispidulin
    99.74%, Pim-1 Inhibitor
    target: Pim
    Research Areas: Cancer