Potential neuroprotective flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora

Bioorg Med Chem Lett. 2013 Sep 15;23(18):5150-4. doi: 10.1016/j.bmcl.2013.07.020. Epub 2013 Jul 19.

Abstract

Rhus parviflora (Anacardiaceae) is an indigenous medicinal shrub found in South Asia with flavonoid rich edible fruit. This study examined flavonoid derivatives of R. parviflora fruit with CDK5/p25 inhibition activity. Evaluation by in vitro assay and docking simulations for CDK5/p25 revealed that the aurones, sulfuretin (1) and aureusidin (2), the aurone glycoside, aureusidin-6-O-β-D-glucopyranoside (3) and hovetrichoside C (4), the flavonoid glycoside, quercetin-3-O-β-D-galactopyranoside (5), and the biflavonoid, cupressuflavone (6), had the potential to inhibit CDK5/p25, which could be useful in the treatment of neurodegenerative disorders such as Alzheimer's disease. Compound2 showed the significant in vitro inhibition capacity (IC50 value of 4.81 μM) as well as binding affinity with docking energy of -8.73 (kcal/mol) for active sites CYS83 and GLN130 of CDK5/p25 enzyme in comparison to reference compound R-roscovitine.

Keywords: AMJCTDBATIKENQ-NXIFTRESSA-N; Alzheimer’s disease; Aureusidin; CDK5/p25; KJIWCKSQHHNTTL-RDBLRTHZSA-N; LADPNODMUXOPRG-UHFFFAOYSA-N; Molecular docking; OVSQVDMCBVZWGM-BOYSSXRUSA-N; RGNXWPVNPFAADO-NSIKDUERSA-N; Rhus parviflora; WBEFUVAYFSOUEA-PQMHYQBVSA-N.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 5 / metabolism
  • Flavonoids / chemical synthesis
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Rhus / chemistry*

Substances

  • Flavonoids
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • TPPP protein, human
  • Cyclin-Dependent Kinase 5