Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies
A new class of indolotacrine hybrids including cyclopenta- and cyclohexa-indolotacrine derivatives was designed, synthesized, and assessed as acetylcholinesterase inhibitors (AChEIs). Some of the designed derivatives indicated a good inhibitory effect against acetylcholinesterase (AChE). Among them,...
Gespeichert in:
| Veröffentlicht in: | Journal of the Iranian Chemical Society 2023-05, Vol.20 (5), p.1049-1060 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1060 |
|---|---|
| container_issue | 5 |
| container_start_page | 1049 |
| container_title | Journal of the Iranian Chemical Society |
| container_volume | 20 |
| creator | Babaee, Saeed Zolfigol, Mohammad Ali Chehardoli, Gholamabbas Faramarzi, Mohammad Ali Mojtabavi, Somayeh Akbarzadeh, Tahmineh Hariri, Roshanak Rastegari, Arezoo Homayouni Moghadam, Farshad Mahdavi, Mohammad Najafi, Zahra |
| description | A new class of indolotacrine hybrids including cyclopenta- and cyclohexa-indolotacrine derivatives was designed, synthesized, and assessed as acetylcholinesterase inhibitors (AChEIs). Some of the designed derivatives indicated a good inhibitory effect against acetylcholinesterase (AChE). Among them, cyclopenta-indolotacrine hybrids showed a slightly better anti-AChE activity than cyclohexa-indolotacrine hybrids. Compound 5-amino-4-(4-chlorophenyl)-2-(1H-indol-3-yl)-4,6,7,8-tetrahydrocyclopenta[b]pyrano[3,2-e]pyridine-3-carbonitrile (
8g
) including 4-chlorophenyl and cyclopentane ring showed the best AChE inhibitory activity with IC
50
value of 0.4 µM. The kinetic study indicated that compound
8g
acted as a competitive inhibitor. Based on molecular docking results, it occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE. Using a neuroprotective assay against H
2
O
2
-induced cell death in PC12 neurons, only compound 8b with 4-methoxyphenyl moiety and cyclopentane ring illustrated significant protection (
P
|
| doi_str_mv | 10.1007/s13738-022-02726-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2807041709</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2807041709</sourcerecordid><originalsourceid>FETCH-LOGICAL-c319t-72458fa5a59513530f327977af54fca34d8b66b4cb84760f3dfd5da4349669d63</originalsourceid><addsrcrecordid>eNp9kM1KxDAUhYsoOI6-gKuA26nmt2ndyeAfiG4U3IU0SduMmWZM2oE-ga9tdBR3wg33wv3OueRk2SmC5whCfhER4aTMIcbpcVzkaC-bIU5Yjiku939nyF8Ps6MYVxAyDhmdZR-PfmscsL32zg9SBdsb0E11sDoCmUqZYXKq8y4t4mCCjCbRna3t4EO8BNpE2_YLEKd-6NIcF6C2yau1SjpgttKNcrA-EbLXYO2dUaOTAWiv3mzfgjiM2pp4nB000kVz8tPn2cvN9fPyLn94ur1fXj3kiqBqyDmmrGwkk6xiiDACG4J5xblsGG2UJFSXdVHUVNUl5UXa6kYzLSmhVVFUuiDz7Gznuwn-fUw_Eis_hj6dFLiEHFLEYZUovKNU8DEG04hNsGsZJoGg-Apc7AIXKXDxHbhASUR2opjgvjXhz_of1ScKl4aE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2807041709</pqid></control><display><type>article</type><title>Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies</title><source>SpringerLink Journals - AutoHoldings</source><creator>Babaee, Saeed ; Zolfigol, Mohammad Ali ; Chehardoli, Gholamabbas ; Faramarzi, Mohammad Ali ; Mojtabavi, Somayeh ; Akbarzadeh, Tahmineh ; Hariri, Roshanak ; Rastegari, Arezoo ; Homayouni Moghadam, Farshad ; Mahdavi, Mohammad ; Najafi, Zahra</creator><creatorcontrib>Babaee, Saeed ; Zolfigol, Mohammad Ali ; Chehardoli, Gholamabbas ; Faramarzi, Mohammad Ali ; Mojtabavi, Somayeh ; Akbarzadeh, Tahmineh ; Hariri, Roshanak ; Rastegari, Arezoo ; Homayouni Moghadam, Farshad ; Mahdavi, Mohammad ; Najafi, Zahra</creatorcontrib><description>A new class of indolotacrine hybrids including cyclopenta- and cyclohexa-indolotacrine derivatives was designed, synthesized, and assessed as acetylcholinesterase inhibitors (AChEIs). Some of the designed derivatives indicated a good inhibitory effect against acetylcholinesterase (AChE). Among them, cyclopenta-indolotacrine hybrids showed a slightly better anti-AChE activity than cyclohexa-indolotacrine hybrids. Compound 5-amino-4-(4-chlorophenyl)-2-(1H-indol-3-yl)-4,6,7,8-tetrahydrocyclopenta[b]pyrano[3,2-e]pyridine-3-carbonitrile (
8g
) including 4-chlorophenyl and cyclopentane ring showed the best AChE inhibitory activity with IC
50
value of 0.4 µM. The kinetic study indicated that compound
8g
acted as a competitive inhibitor. Based on molecular docking results, it occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE. Using a neuroprotective assay against H
2
O
2
-induced cell death in PC12 neurons, only compound 8b with 4-methoxyphenyl moiety and cyclopentane ring illustrated significant protection (
P
< 0.0001) at a concentration of 100 μM compared to quercetin at a concentration of 10 μM (
P
< 0.0001). In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these indolotacrine hybrids can be a very encouraging AChE inhibitor to treat Alzheimer’s disease.</description><identifier>ISSN: 1735-207X</identifier><identifier>EISSN: 1735-2428</identifier><identifier>DOI: 10.1007/s13738-022-02726-1</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Alzheimer's disease ; Analytical Chemistry ; Biochemistry ; Cell death ; Chemical synthesis ; Chemistry ; Chemistry and Materials Science ; Hydrogen peroxide ; Inhibitors ; Inorganic Chemistry ; Molecular docking ; Organic Chemistry ; Original Paper ; Physical Chemistry</subject><ispartof>Journal of the Iranian Chemical Society, 2023-05, Vol.20 (5), p.1049-1060</ispartof><rights>Iranian Chemical Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c319t-72458fa5a59513530f327977af54fca34d8b66b4cb84760f3dfd5da4349669d63</citedby><cites>FETCH-LOGICAL-c319t-72458fa5a59513530f327977af54fca34d8b66b4cb84760f3dfd5da4349669d63</cites><orcidid>0000-0001-8189-1586</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13738-022-02726-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13738-022-02726-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Babaee, Saeed</creatorcontrib><creatorcontrib>Zolfigol, Mohammad Ali</creatorcontrib><creatorcontrib>Chehardoli, Gholamabbas</creatorcontrib><creatorcontrib>Faramarzi, Mohammad Ali</creatorcontrib><creatorcontrib>Mojtabavi, Somayeh</creatorcontrib><creatorcontrib>Akbarzadeh, Tahmineh</creatorcontrib><creatorcontrib>Hariri, Roshanak</creatorcontrib><creatorcontrib>Rastegari, Arezoo</creatorcontrib><creatorcontrib>Homayouni Moghadam, Farshad</creatorcontrib><creatorcontrib>Mahdavi, Mohammad</creatorcontrib><creatorcontrib>Najafi, Zahra</creatorcontrib><title>Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies</title><title>Journal of the Iranian Chemical Society</title><addtitle>J IRAN CHEM SOC</addtitle><description>A new class of indolotacrine hybrids including cyclopenta- and cyclohexa-indolotacrine derivatives was designed, synthesized, and assessed as acetylcholinesterase inhibitors (AChEIs). Some of the designed derivatives indicated a good inhibitory effect against acetylcholinesterase (AChE). Among them, cyclopenta-indolotacrine hybrids showed a slightly better anti-AChE activity than cyclohexa-indolotacrine hybrids. Compound 5-amino-4-(4-chlorophenyl)-2-(1H-indol-3-yl)-4,6,7,8-tetrahydrocyclopenta[b]pyrano[3,2-e]pyridine-3-carbonitrile (
8g
) including 4-chlorophenyl and cyclopentane ring showed the best AChE inhibitory activity with IC
50
value of 0.4 µM. The kinetic study indicated that compound
8g
acted as a competitive inhibitor. Based on molecular docking results, it occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE. Using a neuroprotective assay against H
2
O
2
-induced cell death in PC12 neurons, only compound 8b with 4-methoxyphenyl moiety and cyclopentane ring illustrated significant protection (
P
< 0.0001) at a concentration of 100 μM compared to quercetin at a concentration of 10 μM (
P
< 0.0001). In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these indolotacrine hybrids can be a very encouraging AChE inhibitor to treat Alzheimer’s disease.</description><subject>Alzheimer's disease</subject><subject>Analytical Chemistry</subject><subject>Biochemistry</subject><subject>Cell death</subject><subject>Chemical synthesis</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Hydrogen peroxide</subject><subject>Inhibitors</subject><subject>Inorganic Chemistry</subject><subject>Molecular docking</subject><subject>Organic Chemistry</subject><subject>Original Paper</subject><subject>Physical Chemistry</subject><issn>1735-207X</issn><issn>1735-2428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kM1KxDAUhYsoOI6-gKuA26nmt2ndyeAfiG4U3IU0SduMmWZM2oE-ga9tdBR3wg33wv3OueRk2SmC5whCfhER4aTMIcbpcVzkaC-bIU5Yjiku939nyF8Ps6MYVxAyDhmdZR-PfmscsL32zg9SBdsb0E11sDoCmUqZYXKq8y4t4mCCjCbRna3t4EO8BNpE2_YLEKd-6NIcF6C2yau1SjpgttKNcrA-EbLXYO2dUaOTAWiv3mzfgjiM2pp4nB000kVz8tPn2cvN9fPyLn94ur1fXj3kiqBqyDmmrGwkk6xiiDACG4J5xblsGG2UJFSXdVHUVNUl5UXa6kYzLSmhVVFUuiDz7Gznuwn-fUw_Eis_hj6dFLiEHFLEYZUovKNU8DEG04hNsGsZJoGg-Apc7AIXKXDxHbhASUR2opjgvjXhz_of1ScKl4aE</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Babaee, Saeed</creator><creator>Zolfigol, Mohammad Ali</creator><creator>Chehardoli, Gholamabbas</creator><creator>Faramarzi, Mohammad Ali</creator><creator>Mojtabavi, Somayeh</creator><creator>Akbarzadeh, Tahmineh</creator><creator>Hariri, Roshanak</creator><creator>Rastegari, Arezoo</creator><creator>Homayouni Moghadam, Farshad</creator><creator>Mahdavi, Mohammad</creator><creator>Najafi, Zahra</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-8189-1586</orcidid></search><sort><creationdate>20230501</creationdate><title>Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies</title><author>Babaee, Saeed ; Zolfigol, Mohammad Ali ; Chehardoli, Gholamabbas ; Faramarzi, Mohammad Ali ; Mojtabavi, Somayeh ; Akbarzadeh, Tahmineh ; Hariri, Roshanak ; Rastegari, Arezoo ; Homayouni Moghadam, Farshad ; Mahdavi, Mohammad ; Najafi, Zahra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-72458fa5a59513530f327977af54fca34d8b66b4cb84760f3dfd5da4349669d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alzheimer's disease</topic><topic>Analytical Chemistry</topic><topic>Biochemistry</topic><topic>Cell death</topic><topic>Chemical synthesis</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Hydrogen peroxide</topic><topic>Inhibitors</topic><topic>Inorganic Chemistry</topic><topic>Molecular docking</topic><topic>Organic Chemistry</topic><topic>Original Paper</topic><topic>Physical Chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Babaee, Saeed</creatorcontrib><creatorcontrib>Zolfigol, Mohammad Ali</creatorcontrib><creatorcontrib>Chehardoli, Gholamabbas</creatorcontrib><creatorcontrib>Faramarzi, Mohammad Ali</creatorcontrib><creatorcontrib>Mojtabavi, Somayeh</creatorcontrib><creatorcontrib>Akbarzadeh, Tahmineh</creatorcontrib><creatorcontrib>Hariri, Roshanak</creatorcontrib><creatorcontrib>Rastegari, Arezoo</creatorcontrib><creatorcontrib>Homayouni Moghadam, Farshad</creatorcontrib><creatorcontrib>Mahdavi, Mohammad</creatorcontrib><creatorcontrib>Najafi, Zahra</creatorcontrib><collection>CrossRef</collection><jtitle>Journal of the Iranian Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Babaee, Saeed</au><au>Zolfigol, Mohammad Ali</au><au>Chehardoli, Gholamabbas</au><au>Faramarzi, Mohammad Ali</au><au>Mojtabavi, Somayeh</au><au>Akbarzadeh, Tahmineh</au><au>Hariri, Roshanak</au><au>Rastegari, Arezoo</au><au>Homayouni Moghadam, Farshad</au><au>Mahdavi, Mohammad</au><au>Najafi, Zahra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies</atitle><jtitle>Journal of the Iranian Chemical Society</jtitle><stitle>J IRAN CHEM SOC</stitle><date>2023-05-01</date><risdate>2023</risdate><volume>20</volume><issue>5</issue><spage>1049</spage><epage>1060</epage><pages>1049-1060</pages><issn>1735-207X</issn><eissn>1735-2428</eissn><abstract>A new class of indolotacrine hybrids including cyclopenta- and cyclohexa-indolotacrine derivatives was designed, synthesized, and assessed as acetylcholinesterase inhibitors (AChEIs). Some of the designed derivatives indicated a good inhibitory effect against acetylcholinesterase (AChE). Among them, cyclopenta-indolotacrine hybrids showed a slightly better anti-AChE activity than cyclohexa-indolotacrine hybrids. Compound 5-amino-4-(4-chlorophenyl)-2-(1H-indol-3-yl)-4,6,7,8-tetrahydrocyclopenta[b]pyrano[3,2-e]pyridine-3-carbonitrile (
8g
) including 4-chlorophenyl and cyclopentane ring showed the best AChE inhibitory activity with IC
50
value of 0.4 µM. The kinetic study indicated that compound
8g
acted as a competitive inhibitor. Based on molecular docking results, it occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE. Using a neuroprotective assay against H
2
O
2
-induced cell death in PC12 neurons, only compound 8b with 4-methoxyphenyl moiety and cyclopentane ring illustrated significant protection (
P
< 0.0001) at a concentration of 100 μM compared to quercetin at a concentration of 10 μM (
P
< 0.0001). In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these indolotacrine hybrids can be a very encouraging AChE inhibitor to treat Alzheimer’s disease.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1007/s13738-022-02726-1</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8189-1586</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1735-207X |
| ispartof | Journal of the Iranian Chemical Society, 2023-05, Vol.20 (5), p.1049-1060 |
| issn | 1735-207X 1735-2428 |
| language | eng |
| recordid | cdi_proquest_journals_2807041709 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Alzheimer's disease Analytical Chemistry Biochemistry Cell death Chemical synthesis Chemistry Chemistry and Materials Science Hydrogen peroxide Inhibitors Inorganic Chemistry Molecular docking Organic Chemistry Original Paper Physical Chemistry |
| title | Novel indolotacrine hybrids as acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and molecular docking studies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T17%3A35%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Novel%20indolotacrine%20hybrids%20as%20acetylcholinesterase%20inhibitors:%20design,%20synthesis,%20biological%20evaluation,%20and%20molecular%20docking%20studies&rft.jtitle=Journal%20of%20the%20Iranian%20Chemical%20Society&rft.au=Babaee,%20Saeed&rft.date=2023-05-01&rft.volume=20&rft.issue=5&rft.spage=1049&rft.epage=1060&rft.pages=1049-1060&rft.issn=1735-207X&rft.eissn=1735-2428&rft_id=info:doi/10.1007/s13738-022-02726-1&rft_dat=%3Cproquest_cross%3E2807041709%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2807041709&rft_id=info:pmid/&rfr_iscdi=true |