Synthesis and Biological Evaluation of Benzophenone Derivatives as Poten- tial HIV-1 Inhibitors
文献类型：期刊论文
| 作者 | Zhen YH3; xiaodong.ma@139.com; Wang RR1; Wang CY3; Huang SS3; Ma XD*3; Zheng YT*1; Liu KX3; Song ZD3; Wang P1,2 |
| 刊名 | Medicinal Chemistry
 |
| 出版日期 | 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). |
| 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. |
入库方式： OAI收割
来源：昆明动物研究所
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