Synthesis and Biological Evaluation of Benzophenone Derivatives as Poten- tial HIV-1 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

	Synthesis and Biological Evaluation of Benzophenone Derivatives as Poten- tial HIV-1 Inhibitors
	Zhen YH 3; xiaodong.ma@139.com ; Wang RR 1; Wang CY 3; Huang SS 3; Ma XD3; Zheng YT1; Liu KX 3; Song ZD 3; Wang P 1,2
刊名	Medicinal Chemistry
	2017
卷号	13 期号:X 页码:98-405
关键词	Activity Aids Analogues Benzophenone Hiv-1 Inhibitor
英文摘要	BACKGROUND: Although a number of agents can achieve high response in acquired immunodeficiency syndrome (AIDS) patients, safer and more active HIV inhibitors are still needed for the growing number of patients infected with resistant HIV virus strains. GW678248, is one of the most potent benzophenone derivatives, exhibiting high potency against a panel of HIV-1 virus (wild-type, K103N mutant, Y181C, etc.) at 1 nM/L concentrations. However, the safety issues associated with rash and liver metabolic enzymes ultimately led to discontinue its further development. As a continuation of our structural modifications on this template, in this manuscript, a new series of benzophenones are described as potential HIV inhibitors. METHODS: All the title molecules were synthesized according to the routes in scheme 1 and scheme 2, and were tested for anti-HIV-1 activity using the MTT method. In the molecular simulation, the docking program of AutoDock 4.0.1 in parallel with the default parameters were used. RESULTS: A series of novel benzophenone derivatives (BPs) with nanomolar anti-HIV-1 activity was identified. Of these inhibitors, analogue 10i (EC50 = 2.9 nmol/L), the most active inhibitor, was comparable to the lead compound in inhibiting the wild-type HIV-1 virus. Additionally, analogue 13b, which not only exhibited strong inhibitory activity against the HIV-1 virus (EC50 = 4.2 nmol/L), but also has very low cytotoxicity with a TI value of more than 219178.1 was also discovered. CONCLUSION: This study led to the identification of a series of benzophenone derivatives with nanomolar level of anti-HIV-1 activity. Analogue 10i and analogue 13b, with low cytotoxicity along with high activity are worthy of further development.
语种	英语
资助机构	This work was supported in part by grants from the National Natural Science Foundation of China (No. 81402788; No. 81102483), and the PhD Start-up Fund of Natural Science Foundation of Liaoning Province, China (No. 20141115). ; This work was supported in part by grants from the National Natural Science Foundation of China (No. 81402788; No. 81102483), and the PhD Start-up Fund of Natural Science Foundation of Liaoning Province, China (No. 20141115). ; This work was supported in part by grants from the National Natural Science Foundation of China (No. 81402788; No. 81102483), and the PhD Start-up Fund of Natural Science Foundation of Liaoning Province, China (No. 20141115). ; This work was supported in part by grants from the National Natural Science Foundation of China (No. 81402788; No. 81102483), and the PhD Start-up Fund of Natural Science Foundation of Liaoning Province, China (No. 20141115).
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/12080]
专题	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昆明动物研究所_分子免疫药理学
通讯作者	xiaodong.ma@139.com; zhengyt@mail.kiz.ac.cn
作者单位	1.Key Laboratory of Animal Models and Hu- man Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 2.School of Pharmaceutical Science & Yunnan Key Laboratory of Phar- macology for Natural Products, Kunming Medical University, Kunming 650500, China 3.College of Pharmacy, Dalian Medical University, Dalian 116044, China
推荐引用方式 GB/T 7714	Zhen YH,xiaodong.ma@139.com,Wang RR,et al. Synthesis and Biological Evaluation of Benzophenone Derivatives as Poten- tial HIV-1 Inhibitors[J]. Medicinal Chemistry,2017,13(X):98-405.
APA	Zhen YH.,xiaodong.ma@139.com.,Wang RR.,Wang CY.,Huang SS.,...&zhengyt@mail.kiz.ac.cn.(2017).Synthesis and Biological Evaluation of Benzophenone Derivatives as Poten- tial HIV-1 Inhibitors.Medicinal Chemistry,13(X),98-405.
MLA	Zhen YH,et al."Synthesis and Biological Evaluation of Benzophenone Derivatives as Poten- tial HIV-1 Inhibitors".Medicinal Chemistry 13.X(2017):98-405.