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J Nat Prod. 2015 Aug 28;78(8):1969-76. doi: 10.1021/acs.jnatprod.5b00324. Epub 2015 Aug 14.

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

Author information

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.

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.

PMID:
26275107
DOI:
10.1021/acs.jnatprod.5b00324
[Indexed for MEDLINE]

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