Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 分子免疫药理学

	Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors
	Yang L 1; Wang P 2,4; Pang W 2; Li YG 1; Shen YM 1; Zheng YT[]2; Li X[]1; Wu JF 3; Yang LM 2; Wang RR 2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2016
卷号	24 期号:9 页码:2125-2136
关键词	Hydrazide derivatives Quinoxalinone Selective gelatinase inhibitors Peptidomimetics Anti-HIV activity
通讯作者	zhengyt@mail.kiz.ac.cn ; tjulx2004@sdu.edu.cn
英文摘要	As our ongoing work on research of gelatinase inhibitors, an array of hydrazide-containing peptidomimetic derivatives bearing quinoxalinone as well as spiro-heterocyclic backbones were designed, synthesized, and assayed for their in vitro enzymatic inhibitory effects. The results demonstrated that both the quinoxalinone (series I and II) and 1,4-dithia-7-azaspiro[4,4]nonane-based hydrazide peptidomimetics (series III) displayed remarkably selectivity towards gelatinase A as compared to APN, with IC50 values in the micromole range. Structure-activity relationships were herein briefly discussed. Given evidences have validated that gelatinase inhibition may be contributable to the therapy of HIV-1 infection, all the target compounds were also submitted to the preliminary in vitro anti-HIV-1 evaluation. It resulted that gelatinase inhibition really has positive correlation with anti-HIV-1 activity, especially compounds 4m and 7h, which gave enhanced gelatinase inhibition in comparison with the positive control LY52, and also decent anti-HIV-1 potencies. The FlexX docking results provided a straightforward insight into the binding pattern between inhibitors and gelatinase, as well as the selective inhibition towards gelatinase over APN. Collectively, our research encouraged potent gelatinase inhibitors might be used in the development of anti-HIV-1 agents. And else, compounds 4m and 7h might be promising candidates to be considered for further chemical optimization
收录类别	SCI
资助信息	Authors are greatly thankful to financial supported from the Natural Science Foundation of Shandong Province (ZR2013HM101), China–Australia Centre for Health Sciences Research Program (2015GJ07), the Program for Changjiang Schol- ars and Innovative Research Team in University (PCSIRT, No IRT13028), the Key Scientific and Technological Program of China (2014ZX10005-002), the Natural Science Foundation of China (81102483), the Key Projects of Chinese Academy of Sciences (KFJ-EW-STS-026), Yunnan Applicative and Basic Research Program (2014FB181, 2015FB182, P0120150150).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9656]
专题	昆明动物研究所_分子免疫药理学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji’nan, Shandong 250012, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 3.Institute of Criminal Science and Technology, Ji’nan Public Security Bureau, Ji’nan 250100, China 4.School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China
推荐引用方式 GB/T 7714	Yang L,Wang P,Pang W,et al. Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2016,24(9):2125-2136.
APA	Yang L.,Wang P.,Pang W.,Li YG.,Shen YM.,...&Wang RR.(2016).Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,24(9),2125-2136.
MLA	Yang L,et al."Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 24.9(2016):2125-2136.