Docking Study of Flavonols and Human c-Jun N-terminal Kinase 1

Bulletin of the Korean chemical society

Ki Woong Jeong¹  Yong Seok Heo¹  Jee Young Lee¹  Yangmee Kim¹ 

关键词: JNK1;    Flavonoid;    Apoptosis;    In silico screening;    Docking;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

c-Jun N-terminal kinase 1 (JNK1) is involved in apoptosis, cell differentiation and proliferation. It has been reported that a flavonol, quercetin, induces cell apoptosis and JNK inhibition. In order to understand the interactions of quercetin and JNK1, we performed receptor-oriented pharmacophore based in silico screening and determined a binding model of human JNK1 and quercetin at the ATP binding site of JNK1. 5-OH of A-ring and carbonyl oxygen of C-ring of quercetin participated in hydrogen bonding interactions with backbone of E109 and M111. Additionally, 3`-OH of quercetin formed a hydrogen bond with backbone of I32. One hydrophobic interaction is related on the binding of quercetin to JNK1 with I32, N114, and V158. Based on this model, we conducted a docking study with other 8 flavonols to find possible flavonoids inhibitors of JNK1. We proposed that one flavonols, rhamnetin, can be a potent inhibitor of JNK and 5-OH of A-ring and 3`-OH of B-ring of flavonols are the essential features for JNK1 inhibition.

【 授权许可】

Unknown