Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors
The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3-dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are here demonstrated for the first time to be reversible competitive in...
Published in: | European Journal of Medicinal Chemistry |
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Online Access: | http://hdl.handle.net/11572/175102 https://doi.org/10.1016/j.ejmech.2017.05.019 |
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ftutrentoiris:oai:iris.unitn.it:11572/175102 2024-04-21T07:51:57+00:00 Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors Botić, Tanja Defant, Andrea Zanini, Pietro Žužek, Monika Cecilija Frangež, Robert Janussen, Dorte Kersken, Daniel Knez, Željko Mancini, Ines Sepčić, Kristina Botić, Tanja Defant, Andrea Zanini, Pietro Žužek, Monika Cecilija Frangež, Robert Janussen, Dorte Kersken, Daniel Knez, Željko Mancini, Ine Sepčić, Kristina 2017 STAMPA http://hdl.handle.net/11572/175102 https://doi.org/10.1016/j.ejmech.2017.05.019 eng eng country:FRA info:eu-repo/semantics/altIdentifier/pmid/28505534 info:eu-repo/semantics/altIdentifier/wos/WOS:000403993500024 volume:136 firstpage:294 lastpage:304 numberofpages:11 journal:EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY http://hdl.handle.net/11572/175102 doi:10.1016/j.ejmech.2017.05.019 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85018920580 info:eu-repo/semantics/openAccess Acetylcholinesterase inhibitor Alzheimer's disease Antarctic sponge Discorhabdin Molecular docking Sponge metabolites info:eu-repo/semantics/article 2017 ftutrentoiris https://doi.org/10.1016/j.ejmech.2017.05.019 2024-03-28T00:48:27Z The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3-dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are here demonstrated for the first time to be reversible competitive inhibitors of cholinesterases. They showed Ki for electric eel acetylcholinesterase of 1.6-15.0μM, for recombinant human acetylcholinesterase of 22.8-98.0μM, and for horse serum butyrylcholinesterase of 5.0-76.0μM. These values are promising when compared to the current cholinesterase inhibitors used for treatment of patients with Alzheimer's disease, to counteract the acetylcholine deficiency in the brain. Good correlation was obtained between IC50 data and results by molecular docking calculation on the binding interactions within the acetylcholinesterase active site, which also indicated the moieties in discorhabdin structures involved. To avoid unwanted peripheral side effects that can appear in patients using some acetylcholinesterase inhibitors, electrophysiological experiments were carried out on one of the most active of these compounds, discorhabdin G, which confirmed that it had no detectable undesirable effects on neuromuscular transmission and skeletal muscle function. These findings are promising for development of cholinesterase inhibitors based on the scaffold of discorhabdins, as potential new agents for treatment of patients with Alzheimer's disease. Article in Journal/Newspaper Antarc* Antarctic Antarctic Peninsula Università degli Studi di Trento: CINECA IRIS European Journal of Medicinal Chemistry 136 294 304 |
institution |
Open Polar |
collection |
Università degli Studi di Trento: CINECA IRIS |
op_collection_id |
ftutrentoiris |
language |
English |
topic |
Acetylcholinesterase inhibitor Alzheimer's disease Antarctic sponge Discorhabdin Molecular docking Sponge metabolites |
spellingShingle |
Acetylcholinesterase inhibitor Alzheimer's disease Antarctic sponge Discorhabdin Molecular docking Sponge metabolites Botić, Tanja Defant, Andrea Zanini, Pietro Žužek, Monika Cecilija Frangež, Robert Janussen, Dorte Kersken, Daniel Knez, Željko Mancini, Ines Sepčić, Kristina Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors |
topic_facet |
Acetylcholinesterase inhibitor Alzheimer's disease Antarctic sponge Discorhabdin Molecular docking Sponge metabolites |
description |
The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3-dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are here demonstrated for the first time to be reversible competitive inhibitors of cholinesterases. They showed Ki for electric eel acetylcholinesterase of 1.6-15.0μM, for recombinant human acetylcholinesterase of 22.8-98.0μM, and for horse serum butyrylcholinesterase of 5.0-76.0μM. These values are promising when compared to the current cholinesterase inhibitors used for treatment of patients with Alzheimer's disease, to counteract the acetylcholine deficiency in the brain. Good correlation was obtained between IC50 data and results by molecular docking calculation on the binding interactions within the acetylcholinesterase active site, which also indicated the moieties in discorhabdin structures involved. To avoid unwanted peripheral side effects that can appear in patients using some acetylcholinesterase inhibitors, electrophysiological experiments were carried out on one of the most active of these compounds, discorhabdin G, which confirmed that it had no detectable undesirable effects on neuromuscular transmission and skeletal muscle function. These findings are promising for development of cholinesterase inhibitors based on the scaffold of discorhabdins, as potential new agents for treatment of patients with Alzheimer's disease. |
author2 |
Botić, Tanja Defant, Andrea Zanini, Pietro Žužek, Monika Cecilija Frangež, Robert Janussen, Dorte Kersken, Daniel Knez, Željko Mancini, Ine Sepčić, Kristina |
format |
Article in Journal/Newspaper |
author |
Botić, Tanja Defant, Andrea Zanini, Pietro Žužek, Monika Cecilija Frangež, Robert Janussen, Dorte Kersken, Daniel Knez, Željko Mancini, Ines Sepčić, Kristina |
author_facet |
Botić, Tanja Defant, Andrea Zanini, Pietro Žužek, Monika Cecilija Frangež, Robert Janussen, Dorte Kersken, Daniel Knez, Željko Mancini, Ines Sepčić, Kristina |
author_sort |
Botić, Tanja |
title |
Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors |
title_short |
Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors |
title_full |
Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors |
title_fullStr |
Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors |
title_full_unstemmed |
Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors |
title_sort |
discorhabdin alkaloids from antarctic latrunculia spp. sponges as a new class of cholinesterase inhibitors |
publisher |
country:FRA |
publishDate |
2017 |
url |
http://hdl.handle.net/11572/175102 https://doi.org/10.1016/j.ejmech.2017.05.019 |
genre |
Antarc* Antarctic Antarctic Peninsula |
genre_facet |
Antarc* Antarctic Antarctic Peninsula |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/28505534 info:eu-repo/semantics/altIdentifier/wos/WOS:000403993500024 volume:136 firstpage:294 lastpage:304 numberofpages:11 journal:EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY http://hdl.handle.net/11572/175102 doi:10.1016/j.ejmech.2017.05.019 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85018920580 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1016/j.ejmech.2017.05.019 |
container_title |
European Journal of Medicinal Chemistry |
container_volume |
136 |
container_start_page |
294 |
op_container_end_page |
304 |
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1796935227824668672 |