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Exploring the chemical space around chrysin to develop novel vascular Ca V 1.2 channel blockers, promising vasorelaxant agents
The flavonoid chrysin is an effective vascular Ca 1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a f...
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| Published in: | Archiv der Pharmazie (Weinheim) 2024-11, Vol.357 (11), p.e2400536 |
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| Main Authors: | , , , , , , , , , |
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| Language: | English |
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| container_issue | 11 |
| container_start_page | e2400536 |
| container_title | Archiv der Pharmazie (Weinheim) |
| container_volume | 357 |
| creator | Falbo, Federica Carullo, Gabriele Panti, Alice Spiga, Ottavia Gianibbi, Beatrice Ahmed, Amer Campiani, Giuseppe Ramunno, Anna Aiello, Francesca Fusi, Fabio |
| description | The flavonoid chrysin is an effective vascular Ca
1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to Ca
1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca
antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the Ca
1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular Ca
1.2 channel blockers. |
| doi_str_mv | 10.1002/ardp.202400536 |
| format | article |
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1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to Ca
1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca
antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the Ca
1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular Ca
1.2 channel blockers.</description><identifier>ISSN: 0365-6233</identifier><identifier>EISSN: 1521-4184</identifier><identifier>DOI: 10.1002/ardp.202400536</identifier><identifier>PMID: 39239992</identifier><language>eng</language><publisher>Germany</publisher><subject>Animals ; Calcium Channel Blockers - chemical synthesis ; Calcium Channel Blockers - chemistry ; Calcium Channel Blockers - pharmacology ; Calcium Channels, L-Type - drug effects ; Calcium Channels, L-Type - metabolism ; Flavonoids - chemical synthesis ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Humans ; Male ; Molecular Docking Simulation ; Molecular Structure ; Rats ; Structure-Activity Relationship ; Vasodilator Agents - chemical synthesis ; Vasodilator Agents - chemistry ; Vasodilator Agents - pharmacology</subject><ispartof>Archiv der Pharmazie (Weinheim), 2024-11, Vol.357 (11), p.e2400536</ispartof><rights>2024 Deutsche Pharmazeutische Gesellschaft.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c622-735a5fa9ecf9aa734f3bac8bbeba12dad39e40d4cc12aa0e51048d5f91bdf103</cites><orcidid>0000-0001-6846-5582 ; 0000-0002-1619-3295 ; 0000-0001-5295-9529</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39239992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Falbo, Federica</creatorcontrib><creatorcontrib>Carullo, Gabriele</creatorcontrib><creatorcontrib>Panti, Alice</creatorcontrib><creatorcontrib>Spiga, Ottavia</creatorcontrib><creatorcontrib>Gianibbi, Beatrice</creatorcontrib><creatorcontrib>Ahmed, Amer</creatorcontrib><creatorcontrib>Campiani, Giuseppe</creatorcontrib><creatorcontrib>Ramunno, Anna</creatorcontrib><creatorcontrib>Aiello, Francesca</creatorcontrib><creatorcontrib>Fusi, Fabio</creatorcontrib><title>Exploring the chemical space around chrysin to develop novel vascular Ca V 1.2 channel blockers, promising vasorelaxant agents</title><title>Archiv der Pharmazie (Weinheim)</title><addtitle>Arch Pharm (Weinheim)</addtitle><description>The flavonoid chrysin is an effective vascular Ca
1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to Ca
1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca
antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the Ca
1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular Ca
1.2 channel blockers.</description><subject>Animals</subject><subject>Calcium Channel Blockers - chemical synthesis</subject><subject>Calcium Channel Blockers - chemistry</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels, L-Type - drug effects</subject><subject>Calcium Channels, L-Type - metabolism</subject><subject>Flavonoids - chemical synthesis</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Humans</subject><subject>Male</subject><subject>Molecular Docking Simulation</subject><subject>Molecular Structure</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><subject>Vasodilator Agents - chemical synthesis</subject><subject>Vasodilator Agents - chemistry</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0365-6233</issn><issn>1521-4184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNo9kMtOwzAQRS0EoqWwZYn8ASSM7Titl6gqD6kSCxDbaGI7bSCxIzut2g3fTqpCV1eaOXdGOoTcMkgZAH_AYLqUA88ApMjPyJhJzpKMzbJzMgaRyyTnQozIVYxfACCAy0syEooLpRQfk5_Frmt8qN2K9mtL9dq2tcaGxg61pRj8xplhGvaxdrT31NitbXxHnR-SbjHqTYOBzpF-UpbyAUXnhk3ZeP1tQ7ynXfBtHQ8PBtoH2-AOXU9xZV0fr8lFhU20N385Ie9Pi4_5S7J8e36dPy4TnXOeTIVEWaGyulKIU5FVokQ9K0tbIuMGjVA2A5NpzTgiWMkgmxlZKVaaioGYkPR4VQcfY7BV0YW6xbAvGBQHjcVBY3HSOBTujoVuU7bWnPB_b-IXkfFxig</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Falbo, Federica</creator><creator>Carullo, Gabriele</creator><creator>Panti, Alice</creator><creator>Spiga, Ottavia</creator><creator>Gianibbi, Beatrice</creator><creator>Ahmed, Amer</creator><creator>Campiani, Giuseppe</creator><creator>Ramunno, Anna</creator><creator>Aiello, Francesca</creator><creator>Fusi, Fabio</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-6846-5582</orcidid><orcidid>https://orcid.org/0000-0002-1619-3295</orcidid><orcidid>https://orcid.org/0000-0001-5295-9529</orcidid></search><sort><creationdate>202411</creationdate><title>Exploring the chemical space around chrysin to develop novel vascular Ca V 1.2 channel blockers, promising vasorelaxant agents</title><author>Falbo, Federica ; 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1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to Ca
1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca
antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the Ca
1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular Ca
1.2 channel blockers.</abstract><cop>Germany</cop><pmid>39239992</pmid><doi>10.1002/ardp.202400536</doi><orcidid>https://orcid.org/0000-0001-6846-5582</orcidid><orcidid>https://orcid.org/0000-0002-1619-3295</orcidid><orcidid>https://orcid.org/0000-0001-5295-9529</orcidid></addata></record> |
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| ispartof | Archiv der Pharmazie (Weinheim), 2024-11, Vol.357 (11), p.e2400536 |
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| subjects | Animals Calcium Channel Blockers - chemical synthesis Calcium Channel Blockers - chemistry Calcium Channel Blockers - pharmacology Calcium Channels, L-Type - drug effects Calcium Channels, L-Type - metabolism Flavonoids - chemical synthesis Flavonoids - chemistry Flavonoids - pharmacology Humans Male Molecular Docking Simulation Molecular Structure Rats Structure-Activity Relationship Vasodilator Agents - chemical synthesis Vasodilator Agents - chemistry Vasodilator Agents - pharmacology |
| title | Exploring the chemical space around chrysin to develop novel vascular Ca V 1.2 channel blockers, promising vasorelaxant agents |
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