The multifactorial nature of Alzheimer's disease (AD) offers us a textbook example where parental compounds, mostly marketed, are modified with the aim of improving and/or conferring two or even more biological activities to contrast or less frequently revert the disease's symptoms. This is the case of tacrine and its dimeric derivative bis(7)-tacrine which, for instance, paved the way for the more ..
Target
| Sequence: RecName: Full=Acetylcholinesterase; Short=AChE; Flags: Precursor Description ..   Protein Family: Esterase_lipase Comment .. Gene:ACHE Related Protein 3D Structures |
BioActive Compound: 1
Description:
Title: Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers.
Abstract: The multifactorial nature of Alzheimer's disease (AD) offers us a textbook example where parental compounds, mostly marketed, are modified with the aim of improving and/or conferring two or even more biological activities to contrast or less frequently revert the disease's symptoms. This is the case of tacrine and its dimeric derivative bis(7)-tacrine which, for instance, paved the way for the development of a broad collection of very interesting homo- and heterodimeric structures, conceived in light of the emerging multi-target approach for AD-related drug discovery. As a contribution to the topic, we report here the design, synthesis and biological evaluation of 12 compounds referable to bis(7)-tacrine. In addition to the cholinesterase activity, some of the selected compounds (7-9 and 12) were capable of inhibiting the non-enzymatic function of AChE and/or showed a remarkable activity against BACE1. Thus, the present study outlines a series of newly synthesized molecules, structurally related to bis(7)-tacrine, endowed with extended biological profile in agreement with the emerging multi-target paradigm.
(PMID: 21798635)
Abstract: The multifactorial nature of Alzheimer's disease (AD) offers us a textbook example where parental compounds, mostly marketed, are modified with the aim of improving and/or conferring two or even more biological activities to contrast or less frequently revert the disease's symptoms. This is the case of tacrine and its dimeric derivative bis(7)-tacrine which, for instance, paved the way for the development of a broad collection of very interesting homo- and heterodimeric structures, conceived in light of the emerging multi-target approach for AD-related drug discovery. As a contribution to the topic, we report here the design, synthesis and biological evaluation of 12 compounds referable to bis(7)-tacrine. In addition to the cholinesterase activity, some of the selected compounds (7-9 and 12) were capable of inhibiting the non-enzymatic function of AChE and/or showed a remarkable activity against BACE1. Thus, the present study outlines a series of newly synthesized molecules, structurally related to bis(7)-tacrine, endowed with extended biological profile in agreement with the emerging multi-target paradigm.
(PMID: 21798635)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 93
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 93
ChEMBL target type: Target is a single protein chain
Result Definitions
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| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Ki* | Ki PubChem standard value |  | Float | μM | |
| 2 | BEI | Binding Efficiency Index(nM) | | Float | ||
| 3 | SEI | Surface Efficiency Index(nM) | | Float | ||
| 4 | Ki activity comment | Ki activity comment | String | |||
| 5 | Ki standard flag | Ki standard flag | | Integer | ||
| 6 | Ki qualifier | Ki qualifier | String | |||
| 7 | Ki published value | Ki published value | | Float | nM | |
| 8 | Ki standard value | Ki standard value | | Float | nM | |
| 9 | Ki binding domains | Ki binding domains | String |
* Activity Concentration.
Data Table (Concise)
Classification
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