Frontiers in Medicinal Chemistry

Volume: 7

Cholinesterase Inhibitors Useful for the Treatment of Neurodegenerative Disorders from Natural Sources: Past and Present

Author(s): Monica R. Loizzo, Rosa Tundis, Federica Menichini and Francesco Menichini

Pp: 183-227 (45)

DOI: 10.2174/9781608059706115070008

* (Excluding Mailing and Handling)

Abstract

Alzheimer’s disease (AD) is the most common form of dementia affecting older people (60-80% cases). Besides the neuropathologic hallmark abnormalities that are deposits of the protein fragment β-amyloid (plaques) and twisted strands of the protein tau (tangles), AD is characterized by a consistent deficit in cholinergic neurotransmission, consequently leading to destruction of cholinergic neurons in basal forebrain. Cholinesterases (acetylcholinesterase - AChE, and butyrylcholinesterase - BChE) are serine hydrolases that split acetylcholine (ACh) and terminate its action. Cholinesterase inhibitors increase the levels of ACh and prolong its action. For this reason, they have relevance to the treatment of neurodegenerative disorders. Moreover, AChE inhibition holds a key role to reduce the aggregation of β amyloid and the formation of the neurotoxic fibrils. Recently, researchers move their interest in finding drugs that are able to inhibit both of these events. This chapter covers the current knowledge of natural products as cholinesterase inhibitors and how these compounds could serve as lead compounds for semi-synthetic analogs with improved properties. In particular, studies in the period 2000-2007 and from 2013 until now (2014 first semester) are reported.


Keywords: Acetylcholinesterase, alkaloids, alzheimer’s disease, butyrylcholinesterase, derivatives, neurodegenerative disorders, polyphenols, terpenoids.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309701250 and j.to_ip >=309701250 )) and ((j.from_date <= 1739847722 and j.to_date >= 1739847722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 7211) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309701250 and j.to_ip >=309701250 )) and ((j.from_date <= 1739847722 and j.to_date >= 1739847722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 7211) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309701250 and j.to_ip >=309701250 )) and ((j.from_date <= 1739847722 and j.to_date >= 1739847722 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 7211)
      700μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1696 and `b`.`banner_from_date` <= 1739847722 and `b`.`banner_to_date` >= 1739847722 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.12msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1696
      • 3: 1739847722
      • 4: 1739847722
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='7859c43fc76530ed57122bfbd2cf5677'
      280μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    8Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        3JwCHebv0prMeex6B06SFYuJCGW89pTJ9k1s5kKG
        uc_cart_id
        7859c43fc76530ed57122bfbd2cf5677
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/7211" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/7211
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        array:5 [ "_token" => "3JwCHebv0prMeex6B06SFYuJCGW89pTJ9k1s5kKG" "uc_cart_id" => "7859c43fc76530ed57122bfbd2cf5677" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/7211" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:02:02GET/chapter/72111121910