Bioactivity Focus of alpha-Cyano-4-hydroxycinnamic acid (CHCA) Leads to Effective Multifunctional Aldose Reductase Inhibitors

doi:10.1038/srep24942

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	Bioactivity Focus of alpha-Cyano-4-hydroxycinnamic acid (CHCA) Leads to Effective Multifunctional Aldose Reductase Inhibitors
	Zhang, Laitao 2; Li, Yi-Fang 2,3; Yuan, Sheng 2; Zhang, Shijie 4; Zheng, Huanhuan 2; Liu, Jie 2; Sun, Pinghua 2; Gu, Yijun 1; Kurihara, Hiroshi 2,3; He, Rong-Rong 2,3
刊名	SCIENTIFIC REPORTS
	2016-04-25
卷号	6
ISSN号	2045-2322
DOI	10.1038/srep24942
文献子类	Article
英文摘要	Bioactivity focus on alpha-cyano-4-hydroxycinnamic acid (CHCA) scaffold results in a small library of novel multifunctional aldose reductase (ALR2) inhibitors. All the entities displayed good to excellent inhibition with IC50 72-405 nM. (R,E)-N-(3-(2-acetamido-3-(benzyloxy)propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl) acrylamide (5f) was confirmed as the most active inhibitor (IC50 72.7 +/- 1.6 nM), and the best antioxidant. 5f bound to ALR2 with new mode without affecting the aldehyde reductase (ALR1) activity, implicating high selectivity to ALR2. 5f was demonstrated as both an effective ALR2 inhibitor (ARI) and antioxidant in a chick embryo model of hyperglycemia. It attenuated hyperglycemia-induced incidence of neural tube defects (NTD) and death rate, and significantly improved the body weight and morphology of the embryos. 5f restored the expression of paired box type 3 transcription factor (Pax3), and reduced the hyperglycemia-induced increase of ALR2 activity, sorbitol accumulation, and the generation of ROS and MDA to normal levels. All the evidences support that 5f may be a potential agent to treat diabetic complications.
资助项目	National Natural Science Foundation of China[81172982] ; National Natural Science Foundation of China[81402981] ; State Key Laboratory of Drug Research[SIMM1501KF-14] ; Science and Technology Program of Guangzhou[2012J22000073] ; Fundamental Research Funds for the Central Universities[21614303]
WOS关键词	DIABETIC PERIPHERAL NEUROPATHY ; P-COUMARIC ACID ; FIDARESTAT SNK-860 ; CURCUMIN ANALOGS ; POTENTIAL AGENTS ; GENE-EXPRESSION ; NEURAL-TUBE ; IN-VITRO ; COMPLICATIONS ; XANTHONES
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000374642500003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276067]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	He, Rong-Rong; Chen, Heru
作者单位	1.Natl Ctr Prot Sci Shanghai, Shanghai 201210, Peoples R China; 2.Jinan Univ, Inst Tradit Chinese Med & Nat Prod, Coll Pharm, Guangzhou 510632, Guangdong, Peoples R China; 3.Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou 510632, Guangdong, Peoples R China; 4.Guangzhou Univ Chinese Med, Inst Clin Pharmacol, Guangzhou 510006, Guangdong, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Laitao,Li, Yi-Fang,Yuan, Sheng,et al. Bioactivity Focus of alpha-Cyano-4-hydroxycinnamic acid (CHCA) Leads to Effective Multifunctional Aldose Reductase Inhibitors[J]. SCIENTIFIC REPORTS,2016,6.
APA	Zhang, Laitao.,Li, Yi-Fang.,Yuan, Sheng.,Zhang, Shijie.,Zheng, Huanhuan.,...&Chen, Heru.(2016).Bioactivity Focus of alpha-Cyano-4-hydroxycinnamic acid (CHCA) Leads to Effective Multifunctional Aldose Reductase Inhibitors.SCIENTIFIC REPORTS,6.
MLA	Zhang, Laitao,et al."Bioactivity Focus of alpha-Cyano-4-hydroxycinnamic acid (CHCA) Leads to Effective Multifunctional Aldose Reductase Inhibitors".SCIENTIFIC REPORTS 6(2016).