Potential neuroprotective flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora.
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.
Graduate School of Biotechnology, Institute of Life Sciences and Resources, Kyung Hee University, Yongin 446-701, Republic of Korea.
Sabina
S
Shrestha
Sathishkumar
S
Natarajan
Ji-Hae
JH
Park
Dae-Young
DY
Lee
Jin-Gyeong
JG
Cho
Geum-Soog
GS
Kim
Yong-Jin
YJ
Jeon
Seung-Woo
SW
Yeon
Deok-Chun
DC
Yang
Nam-In
NI
Baek
D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D029045:Rhus / Q000737:chemistry*
D005419:Flavonoids; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C118136:TPPP protein, human; D051360:Cyclin-Dependent Kinase 5
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