Graduate School of Biotechnology, Institute of Life Sciences and Resources, Kyung Hee University, Yongin 446-701, Republic of Korea.
Bioorg Med Chem Lett. 2013 Sep 15;23(18):5150-4. doi: 10.1016/j.bmcl.2013.07.020. Epub 2013 Jul 19.
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.
野鸦椿（漆树科）是一种在南亚发现的含有丰富类黄酮的可食用药用灌木。本研究检测了具有 CDK5/p25 抑制活性的野鸦椿果实中的类黄酮衍生物。通过体外试验和对接模拟对 CDK5/p25 的评估表明，橙酮类化合物硫磺素（1）和金缕梅黄素（2）、橙酮糖苷金缕梅黄素-6-O-β-D-吡喃葡萄糖苷（3）和厚朴脂素 C（4）、黄酮糖苷槲皮素-3-O-β-D-半乳糖苷（5）和双黄酮类化合物扁柏双黄酮（6）具有抑制 CDK5/p25 的潜力，这可能对治疗阿尔茨海默病等神经退行性疾病有用。与对照化合物 R-罗克洛维汀相比，化合物 2 显示出显著的体外抑制能力（IC50 值为 4.81 μM）以及与 CDK5/p25 酶的活性位点 CYS83 和 GLN130 的结合亲和力，对接能为-8.73（kcal/mol）。
