Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors

Wang, Bin; Mai, Yi-Chi; Li, Yue; Hou, Jinqiang; Huang, Shi‐Liang; Ou, Tian‐Miao; Tan, Jia‐Heng; An, Lin‐Kun; Ding, Li; Gu, Lian‐Quan; Huang, Zhi‐Shu

doi:10.1016/j.ejmech.2009.12.044

Cited by 53 publications

(30 citation statements)

References 19 publications

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“…42 Some of these synthetic analogs have included structural features of the AChE inhibitor tacrine but disappointingly, showed greater selectivity for BChE, 43 whilst other 3-aminoalkanamido-substituted 7,8-dehydrorutaecarpine derivatives ( 10 , 11 and 12 ) were more potent and showed selectivity for AChE. 44 Of four bisindole alkaloids isolated from the root of Tabernaemontana divaricata (L.) R. Br. ex Roem.…”

Section: Acetylcholinesterase Inhibitors (Cholinergic Hypothesis)mentioning

confidence: 99%

Natural products as a source of Alzheimer's drug leads

2011

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Section: Acetylcholinesterase Inhibitors (Cholinergic Hypothesis)mentioning

confidence: 99%

Natural products as a source of Alzheimer's drug leads

2011

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“…In quest of the properties in°uencing the activity, 2D-QSAR models was generated and validated using a set of 52 compounds from the literature. [18][19][20] Uni-Column statistics was applied on the training and test set and the results are indicated in Table 2. Various 2D-QSAR models were generated and the best model [M1] was selected on the basis of statistical parameters squared correlation coe±cient (r 2 ), crossed validated ðq 2 Þ, which is a relative measure of quality of¯t, Fischer's value F -test which represents F -ratio between the variance of calculated and observed activity and squared correlation coe±cient r 2 for the test set (pred r 2 ).…”

Section: D-qsar Analysismentioning

confidence: 99%

“…17 In the present compilation, a dataset of diverse AChEIs has been taken for the development of prediction models from the literature. [18][19][20] 2D and kNN-molecular eld analysis models have been developed using 2D and 3D-modules of VLife respectively. [21][22][23] Further, the binding mode of the active derivatives with the active site has been performed by docking with Vlife, [21][22][23] ArgusLab 24 and Autodock 25,26 softwares.…”

Section: Introductionmentioning

confidence: 99%

Understanding the quantitative structure–activity relationship of acetylcholinesterase inhibitors for the treatment of Alzheimer's disease

Sharma

Piplani

2015

J. Theor. Comput. Chem.

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Alzheimer's disease (AD) is the most common cause of dementia in old aged people and clinically used drugs for treatment are associated with side e®ects. Thus, there is a current demand for the discovery and development of new potential molecules. However, the recent advances in drug therapy have challenged the predominance of the disease. In this manuscript, an attempt has been made to develop the 2D and 3D quantitative structure-activity relationship (QSAR) models for a series of rutaecarpine, quinazolines and 7,8-dehydrorutaecarpine derivatives to obtain insights to Acetylcholinesterase (AChE) inhibition. Five di®erent QSAR models have been generated and validated using a set of 52 compounds comprising of varying sca®olds with IC 50 values ranging from 11,000 nM to 0.6 nM. These AChE-speci¯c prediction models (M1-M5) adequately re°ect the structure-activity relationship of the existing AChE inhibitors. Out of all developed models, QSAR model generated using ADME properties has been found to be the best with satisfactory statistical signi¯cance (regression (r 2 ) of 0.9309 and regression adjusted coe±cient of variation (r 2 adj ) of 0.9194). The QSAR models highlight the importance of aromatic moiety as their presence in the structure in°uence the biological activity. Additional insights on the compounds show that acyclic amines attached to side chain have lower activity than cyclic amines. The QSAR models pinpointing structural basis for the AChEIs suggest new guidelines for the design of novel molecules.

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“…And recent reports suggested that increasing acetylcholinesterase (AChE) inhibition and simultaneously improving selectivity for AChE over butyrylcholinesterase (BuChE) would be a promising direction for AD treatment. 11 The crystal structure of AChE indicated that AChE possessed two binding sites: a catalytic active site (CAS) was located at the bottom of the deep narrow gorge and a peripheral anionic site (PAS) at the entrance. The PAS was found to be related with the non-catalytic function of AChE, accelerating β-amyloid (Aβ) peptide deposition and promoting the formation of Aβ fibril.…”

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confidence: 99%