616885-86-0Relevant articles and documents
Design, synthesis and evaluation of scutellarein-O-acetamidoalkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease
Sang, Zhipei,Qiang, Xiaoming,Li, Yan,Xu, Rui,Cao, Zhongcheng,Song, Qing,Wang, Ting,Zhang, Xiaoyu,Liu, Hongyan,Tan, Zhenghuai,Deng, Yong
, p. 307 - 323 (2017)
A series of scutellarein-O-acetamidoalkylbenzylamines derivatives were designed based on a multitarget-directed ligands strategy for the treatment of Alzheimer's disease. Among these compounds, compound T-22 demonstrated excellent acetylcholinesterase inhibitory, moderate inhibitory effects on self-induced Aβ1-42 aggregation, Cu2+-induced Aβ1-42 aggregation, human AChE-induced Aβ1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Aβ1-42 fibrils, and also acted as potential antioxidant and biometals chelator. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that T-22 interacted with both the catalytic active site and peripheral anionic site of AChE. Moreover, compound T-22 showed a good neuroprotective effect against H2O2-induced PC12?cell injury and low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated T-22 significantly reversed scopolamine-induced memory deficit in mice. Taken together, the data showed that T-22 was an interesting multifunctional lead compound worthy of further study for AD.
Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation
Song, Qing,Li, Yan,Cao, Zhongcheng,Qiang, Xiaoming,Tan, Zhenghuai,Deng, Yong
, p. 137 - 149 (2018/11/30)
A series of salicylamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors. They showed good inhibitory activities of self- and Cu2+-induced Aβ1–42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward RatAChE and EeAChE with IC50 value of 10.4 μM and 15.2 μM, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu2+-induced Aβ1–42 aggregation inhibitory potency (42.5% and 31.4% at 25.0 μM, respectively) and moderate disaggregation ability to self- and Cu2+-induced Aβ1–42 aggregation fibrils (23.4% and 27.0% at 25 μM, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment.
Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
Pan, Wanli,Hu, Ke,Bai, Ping,Yu, Lintao,Ma, Qinge,Li, Tao,Zhang, Xu,Chen, Changzhong,Peng, Kelin,Liu, Wenmin,Sang, Zhipei
, p. 2539 - 2543 (2016/07/07)
A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7 μM) and self-induced β-amyloid (Aβ1-42) aggregation (30.8-39.1%, 25 μM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50 = 3.2 μM), and Aβ1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aβ aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.
Pterostilbene-O-acetamidoalkylbenzylamines derivatives as novel dual inhibitors of cholinesterase with anti-β-amyloid aggregation and antioxidant properties for the treatment of Alzheimer's disease
Li, Yuxing,Qiang, Xiaoming,Li, Yan,Yang, Xia,Luo, Li,Xiao, Ganyuan,Cao, Zhongcheng,Tan, Zhenghuai,Deng, Yong
supporting information, p. 2035 - 2039 (2016/04/05)
A series of pterostilbene-O-acetamidoalkylbenzylamines were designed, synthesized and evaluated as dual inhibitors of AChE and BuChE. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and inhibitory effects on self-induced Aβ1-42 aggregation and HuAChE-induced Aβ1-40 aggregation were also tested. The results showed that most of these compounds could effectively inhibit AChE and BuChE. Particularly, compound 21d exhibited the best AChE inhibitory activity (IC50 = 0.06 μM) and good inhibition of BuChE (IC50 = 28.04 μM). Both the inhibition kinetic analysis and molecular modeling study revealed that these compounds showed mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activity. However, the inhibitory activities against self-induced and HuAChE-induced Aβ aggregation of these new derivatives were unsatisfied. Taking into account the results of the biological evaluation, further modifications will be designed in order to increase the potency on the different targets. The results displayed in this Letter can be a new starting point for further development of multifunctional agents for Alzheimer's disease.
Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer's disease
Liu, Qiang,Qiang, Xiaoming,Li, Yan,Sang, Zhipei,Li, Yuxing,Tan, Zhenghuai,Deng, Yong
, p. 911 - 923 (2015/03/04)
A series of chromone-2-carboxamido-alkylbenzylamines were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 49 displayed excellent inhibitory potency toward acetylcholinesterase (AChE), moderate anti-oxidative activity, selective biometal chelating, and possessed good inhibitory effects on self-induced and Cu2+-induced Aβ aggregation. Both kinetic analysis of AChE inhibition and molecular modeling study indicated that 49 was a mixed-type inhibitor, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. These results suggested that 49 might be a potential multifunctional agent for AD treatment.
2, 5-Bis-Diamine [1,4] Benzoquinone-Derivatives
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Page/Page column 14, (2009/04/24)
Synthesis of 2,5-bis-diamine-[1,4]benzoquinonic derivatives having the general formula (I), products and intermediates of said synthesis; the synthesis involves the use of p-benzoquinones having the general formula (IX) and diamines having the general for
Useful for treating neuropraxia Alzheimer 2, 5-BIS-Dimamine-[ 1, 4] Benzoquinonimine derivative, and a method for manufacturing the same, and a method for manufacturing the intermediate body
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Page/Page column 17, (2008/06/13)
2,5-bis-diamine-[1,4]benzoquinonic derivatives, having a general formula (I) have proved useful for the treatment of Alzheimer's disease; a method for preparing them and intermediates used in said method are also described.
