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

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.

• Authors: Sabina Shrestha, Sathishkumar Natarajan, Ji-Hae Park, Dae-Young Lee, Jin-Gyeong Cho, Geum-Soog Kim, Yong-Jin Jeon, Seung-Woo Yeon, Deok-Chun Yang, Nam-In Baek
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 18 Pg. 5150-4 (Sep 15 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23927974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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