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Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia

文献类型：期刊论文

作者Yang, Gui-Xiang1; Sun, Jia-Min1; Zheng, Lu-Lu1; Zhang, Li1; Li, Jie1; Gan, Hai-Xian1; Huang, Yan1; Huang, Jin1; Diao, Xing-Xing2; Tang, Yun1
刊名BIOORGANIC & MEDICINAL CHEMISTRY
出版日期2021-05-01
卷号37页码:16
关键词Vascular dementia Diosgenin Antioxidant Anti-cholinesterase Multi-target-directed ligands
ISSN号0968-0896
DOI10.1016/j.bmc.2021.116109
通讯作者Tang, Yun(ytang234@ecust.edu.cn) ; Wang, Rui(ruiwang@ecust.edu.cn) ; Ma, Lei(malei@ecust.edu.cn)
英文摘要A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
资助项目National Natural Science Foundation of China[81973196] ; National Natural Science Foundation of China[81673318] ; 111 Project[BP0719034] ; Natural Science Foundation of Shanghai[19ZR1413900]
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:000639159300002
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/296560]  
专题中国科学院上海药物研究所
通讯作者Tang, Yun; Wang, Rui; Ma, Lei
作者单位1.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Gui-Xiang,Sun, Jia-Min,Zheng, Lu-Lu,et al. Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2021,37:16.
APA Yang, Gui-Xiang.,Sun, Jia-Min.,Zheng, Lu-Lu.,Zhang, Li.,Li, Jie.,...&Ma, Lei.(2021).Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia.BIOORGANIC & MEDICINAL CHEMISTRY,37,16.
MLA Yang, Gui-Xiang,et al."Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia".BIOORGANIC & MEDICINAL CHEMISTRY 37(2021):16.

入库方式： OAI收割

来源：上海药物研究所

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