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Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents.
Bioorg Med Chem. 2013 Dec 01; 21(23):7275-82.BM

Abstract

A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 μM for AChE and 0.82-11.45 μM for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aβ aggregation inhibitory activity at 20 μM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.

Authors+Show Affiliations

Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, People's Republic of China. Electronic address: luowen83@henu.edu.cn.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24148835

Citation

Luo, Wen, et al. "Design, Synthesis and Evaluation of Novel 4-dimethylamine Flavonoid Derivatives as Potential Multi-functional anti-Alzheimer Agents." Bioorganic & Medicinal Chemistry, vol. 21, no. 23, 2013, pp. 7275-82.
Luo W, Su YB, Hong C, et al. Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents. Bioorg Med Chem. 2013;21(23):7275-82.
Luo, W., Su, Y. B., Hong, C., Tian, R. G., Su, L. P., Wang, Y. Q., Li, Y., Yue, J. J., & Wang, C. J. (2013). Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents. Bioorganic & Medicinal Chemistry, 21(23), 7275-82. https://doi.org/10.1016/j.bmc.2013.09.061
Luo W, et al. Design, Synthesis and Evaluation of Novel 4-dimethylamine Flavonoid Derivatives as Potential Multi-functional anti-Alzheimer Agents. Bioorg Med Chem. 2013 Dec 1;21(23):7275-82. PubMed PMID: 24148835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents. AU - Luo,Wen, AU - Su,Ya-Bin, AU - Hong,Chen, AU - Tian,Run-Guo, AU - Su,Lei-Peng, AU - Wang,Yue-Qiao, AU - Li,Yang, AU - Yue,Jun-Jie, AU - Wang,Chao-Jie, Y1 - 2013/10/04/ PY - 2013/08/07/received PY - 2013/09/24/revised PY - 2013/09/25/accepted PY - 2013/10/24/entrez PY - 2013/10/24/pubmed PY - 2014/5/20/medline KW - Anti-Alzheimer agent KW - Antioxidation KW - Cholinesterase KW - Flavonoid derivatives KW - Self-induced Aβ aggregation SP - 7275 EP - 82 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 21 IS - 23 N2 - A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 μM for AChE and 0.82-11.45 μM for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aβ aggregation inhibitory activity at 20 μM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/24148835/Design_synthesis_and_evaluation_of_novel_4_dimethylamine_flavonoid_derivatives_as_potential_multi_functional_anti_Alzheimer_agents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(13)00850-X DB - PRIME DP - Unbound Medicine ER -