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Synthesis and biological activity evaluation of phthalimide-donepezil hybrids
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Jun-jie WANG1, 2, Ye-shu MU2, 3, Chen HONG1, *, Wen LUO2, *
Acta Pharmaceutica Sinica | 2024, 59(3) : 651 - 660
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Acta Pharmaceutica Sinica | 2024, 59(3): 651-660
• Original Articles •
Synthesis and biological activity evaluation of phthalimide-donepezil hybrids
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Jun-jie WANG1, 2, Ye-shu MU2, 3, Chen HONG1, *, Wen LUO2, *
Affiliations
  • 1. Huaihe Hospital, Henan University, Kaifeng 475004, China
  • 2. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China
  • 3. School of Pharmacy, Henan University, Kaifeng 475004, China
Published: 2024-03-12 doi: 10.16438/j.0513-4870.2023-0863
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A series of phthalimide-donepezil (PTA-DPZ) hybrids (5a-e, 6a-l) were designed, synthesized and evaluated as selective inhibitors of acetylcholinesterase (AChE). The results showed that some hybrids had strong AChE inhibitory activity with half maximal inhibitory concentration (IC50) at nanomolar range, which was better than the control drugs galanthamine and tacrine, and equivalent to DPZ. Compound 6k exhibited the strongest inhibition to AChE with an IC50 value of 0.13 μmol·L-1. Kinetic and molecular modeling studies showed that 6k targeted both catalytic active site and peripheral anionic site of AChE. Moreover, some compounds could inhibit AChE-induced β-amyloid (Aβ) aggregation. In addition, absorption, distribution, metabolism and excretion prediction results showed 6k conforms to the Lipinski's rule of five and had high partition coefficient P value. These compounds, especially 6k, may be considered as a dual-functional lead compound for in-depth research.

phthalimide  /  donepezil  /  cholinesterase  /  β-amyloid  /  Alzheimer's disease
Jun-jie WANG, Ye-shu MU, Chen HONG, Wen LUO. Synthesis and biological activity evaluation of phthalimide-donepezil hybrids[J]. Acta Pharmaceutica Sinica, 2024 , 59 (3) : 651 -660 . DOI: 10.16438/j.0513-4870.2023-0863
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Article Info
doi: 10.16438/j.0513-4870.2023-0863
  • Receive Date：2023-07-13
  • Online Date：2025-11-28
  • Published：2024-03-12
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History
  • Received：2023-07-13
  • Revised：2023-09-26
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Affiliations
    1. Huaihe Hospital, Henan University, Kaifeng 475004, China
    2. Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China
    3. School of Pharmacy, Henan University, Kaifeng 475004, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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