4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L

Fitoterapia. 2019 Jan;132:26-29. doi: 10.1016/j.fitote.2018.08.005. Epub 2018 Aug 13.

Abstract

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88 ± 0.18 μM and 3.19 ± 0.07 μM, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Ki = 12.8 ± 0.6 μM and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with Ki = 322 ± 33 μM, αKi = 133 ± 15 μM, βKi = 5.14 ± 0.41 μM and γKi = 13.2 ± 13 μM.

Keywords: Cathepsin inhibition; Cooperativity inhibition; Dulacia egleri; Flavonoid; Nucleosides.

MeSH terms

  • Brazil
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin L / antagonists & inhibitors*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / chemistry*
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology
  • Molecular Structure
  • Olacaceae / chemistry*
  • Plant Leaves / chemistry

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Cathepsin B
  • Cathepsin L