Pronounced Anti‐Inflammatory and Analgesic Activities of a Spirofuran‐Triazolo[1,5‐a]pyrimidine Scaffold Available via Biginelli Multicomponent Condensation
In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT ass...
Gespeichert in:
| Veröffentlicht in: | ChemistrySelect (Weinheim) 2024-09, Vol.9 (36), p.n/a |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 36 |
| container_start_page | |
| container_title | ChemistrySelect (Weinheim) |
| container_volume | 9 |
| creator | Gümüş, Mustafa Kemal Doğan, İnci Selin Reis, Rengin Sipahi, Hande Uba, Abdullahi Ibrahim Gorobets, Mykola Yu |
| description | In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT assay. Then, those with cell viability higher than 70 % were tested for their anti‐inflammatory activity at their non‐toxic doses by evaluating the nitrite level of the cell supernatants with the Griess reagent. Compounds 5 b, 5 d, 5 e, and 5 g demonstrated significant inhibition of nitrite production by 49 %, 59 %, 63 % respectively at 100 μM (p |
| doi_str_mv | 10.1002/slct.202402286 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_slct_202402286</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>SLCT202402286</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1746-a9702b7e5dcf588b749d509f1e04bf8a3ccecc41268c28d88852507d4f91a3463</originalsourceid><addsrcrecordid>eNqFkM9KAzEQxhdRsNRePecBbE3SzW72WIt_ChWF1pPIMs0mZSRNSrKtrCcfwWfw0XwSt1TUm6eZ-WZ-H8OXJKeMDhil_DxaVQ845SnlXGYHSYcPM9HPRFoc_umPk16Mz5RSlsmMi7yTfNwH7_zGKV2Rkavx8-194oyF1QpqHxoCbqeDXeqIioxUjVusUUfiDQEyW2PwZhPAtdw8ILx66x_ZmWhHeFo3AVdYodNkpsAYb1uvLaCFhdVki0AucNlurUVyu7E1Kr9ae6ddTcbeVdpFqNG7k-TIgI269127ycPV5Xx805_eXU_Go2lfsTzN-lDklC9yLSplhJSLPC0qQQvDNE0XRsJQKa1UyngmFZeVlFJwQfMqNQWDYZoNu8lg76uCjzFoU67b_yE0JaPlLuRyF3L5E3ILFHvgBa1u_rkuZ9Px_Jf9ArKLiCk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Pronounced Anti‐Inflammatory and Analgesic Activities of a Spirofuran‐Triazolo[1,5‐a]pyrimidine Scaffold Available via Biginelli Multicomponent Condensation</title><source>Access via Wiley Online Library</source><creator>Gümüş, Mustafa Kemal ; Doğan, İnci Selin ; Reis, Rengin ; Sipahi, Hande ; Uba, Abdullahi Ibrahim ; Gorobets, Mykola Yu</creator><creatorcontrib>Gümüş, Mustafa Kemal ; Doğan, İnci Selin ; Reis, Rengin ; Sipahi, Hande ; Uba, Abdullahi Ibrahim ; Gorobets, Mykola Yu</creatorcontrib><description>In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT assay. Then, those with cell viability higher than 70 % were tested for their anti‐inflammatory activity at their non‐toxic doses by evaluating the nitrite level of the cell supernatants with the Griess reagent. Compounds 5 b, 5 d, 5 e, and 5 g demonstrated significant inhibition of nitrite production by 49 %, 59 %, 63 % respectively at 100 μM (p<0.05), whereas 56 % inhibition was seen with 50 μM of 5 g. According to the inhibition of PGE2, compound 5 b showed the most notable effect compared to control. All tested compounds, particularly 5 b, 5 d, 5 e and 5 f reduced the PGE2 level and showed potential analgesic activity. Seven heterocycles 5 a–g showed moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of 5 a–i with COX‐1. Instead, the modelling results also show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2. However, the simulation distinguished the key role of the 2‐OH group in stabilizing the inhibitor‐target complex only in the case of binding to COX‐2.
A series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) are evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. Compounds 5 a–g show moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of compounds 5 a–i with COX‐1. Instead, the modelling results show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2.</description><identifier>ISSN: 2365-6549</identifier><identifier>EISSN: 2365-6549</identifier><identifier>DOI: 10.1002/slct.202402286</identifier><language>eng</language><subject>Anti-inflammatory activity ; Biginelli reaction ; Molecular docking ; MTT assay ; PGE2</subject><ispartof>ChemistrySelect (Weinheim), 2024-09, Vol.9 (36), p.n/a</ispartof><rights>2024 Wiley-VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1746-a9702b7e5dcf588b749d509f1e04bf8a3ccecc41268c28d88852507d4f91a3463</cites><orcidid>0000-0001-8089-4646 ; 0000-0002-3484-2201 ; 0000-0001-6373-5221 ; 0000-0001-6482-3143 ; 0000-0003-4949-1747 ; 0000-0002-0853-108X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fslct.202402286$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fslct.202402286$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids></links><search><creatorcontrib>Gümüş, Mustafa Kemal</creatorcontrib><creatorcontrib>Doğan, İnci Selin</creatorcontrib><creatorcontrib>Reis, Rengin</creatorcontrib><creatorcontrib>Sipahi, Hande</creatorcontrib><creatorcontrib>Uba, Abdullahi Ibrahim</creatorcontrib><creatorcontrib>Gorobets, Mykola Yu</creatorcontrib><title>Pronounced Anti‐Inflammatory and Analgesic Activities of a Spirofuran‐Triazolo[1,5‐a]pyrimidine Scaffold Available via Biginelli Multicomponent Condensation</title><title>ChemistrySelect (Weinheim)</title><description>In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT assay. Then, those with cell viability higher than 70 % were tested for their anti‐inflammatory activity at their non‐toxic doses by evaluating the nitrite level of the cell supernatants with the Griess reagent. Compounds 5 b, 5 d, 5 e, and 5 g demonstrated significant inhibition of nitrite production by 49 %, 59 %, 63 % respectively at 100 μM (p<0.05), whereas 56 % inhibition was seen with 50 μM of 5 g. According to the inhibition of PGE2, compound 5 b showed the most notable effect compared to control. All tested compounds, particularly 5 b, 5 d, 5 e and 5 f reduced the PGE2 level and showed potential analgesic activity. Seven heterocycles 5 a–g showed moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of 5 a–i with COX‐1. Instead, the modelling results also show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2. However, the simulation distinguished the key role of the 2‐OH group in stabilizing the inhibitor‐target complex only in the case of binding to COX‐2.
A series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) are evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. Compounds 5 a–g show moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of compounds 5 a–i with COX‐1. Instead, the modelling results show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2.</description><subject>Anti-inflammatory activity</subject><subject>Biginelli reaction</subject><subject>Molecular docking</subject><subject>MTT assay</subject><subject>PGE2</subject><issn>2365-6549</issn><issn>2365-6549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkM9KAzEQxhdRsNRePecBbE3SzW72WIt_ChWF1pPIMs0mZSRNSrKtrCcfwWfw0XwSt1TUm6eZ-WZ-H8OXJKeMDhil_DxaVQ845SnlXGYHSYcPM9HPRFoc_umPk16Mz5RSlsmMi7yTfNwH7_zGKV2Rkavx8-194oyF1QpqHxoCbqeDXeqIioxUjVusUUfiDQEyW2PwZhPAtdw8ILx66x_ZmWhHeFo3AVdYodNkpsAYb1uvLaCFhdVki0AucNlurUVyu7E1Kr9ae6ddTcbeVdpFqNG7k-TIgI269127ycPV5Xx805_eXU_Go2lfsTzN-lDklC9yLSplhJSLPC0qQQvDNE0XRsJQKa1UyngmFZeVlFJwQfMqNQWDYZoNu8lg76uCjzFoU67b_yE0JaPlLuRyF3L5E3ILFHvgBa1u_rkuZ9Px_Jf9ArKLiCk</recordid><startdate>20240925</startdate><enddate>20240925</enddate><creator>Gümüş, Mustafa Kemal</creator><creator>Doğan, İnci Selin</creator><creator>Reis, Rengin</creator><creator>Sipahi, Hande</creator><creator>Uba, Abdullahi Ibrahim</creator><creator>Gorobets, Mykola Yu</creator><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-8089-4646</orcidid><orcidid>https://orcid.org/0000-0002-3484-2201</orcidid><orcidid>https://orcid.org/0000-0001-6373-5221</orcidid><orcidid>https://orcid.org/0000-0001-6482-3143</orcidid><orcidid>https://orcid.org/0000-0003-4949-1747</orcidid><orcidid>https://orcid.org/0000-0002-0853-108X</orcidid></search><sort><creationdate>20240925</creationdate><title>Pronounced Anti‐Inflammatory and Analgesic Activities of a Spirofuran‐Triazolo[1,5‐a]pyrimidine Scaffold Available via Biginelli Multicomponent Condensation</title><author>Gümüş, Mustafa Kemal ; Doğan, İnci Selin ; Reis, Rengin ; Sipahi, Hande ; Uba, Abdullahi Ibrahim ; Gorobets, Mykola Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1746-a9702b7e5dcf588b749d509f1e04bf8a3ccecc41268c28d88852507d4f91a3463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Anti-inflammatory activity</topic><topic>Biginelli reaction</topic><topic>Molecular docking</topic><topic>MTT assay</topic><topic>PGE2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gümüş, Mustafa Kemal</creatorcontrib><creatorcontrib>Doğan, İnci Selin</creatorcontrib><creatorcontrib>Reis, Rengin</creatorcontrib><creatorcontrib>Sipahi, Hande</creatorcontrib><creatorcontrib>Uba, Abdullahi Ibrahim</creatorcontrib><creatorcontrib>Gorobets, Mykola Yu</creatorcontrib><collection>CrossRef</collection><jtitle>ChemistrySelect (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gümüş, Mustafa Kemal</au><au>Doğan, İnci Selin</au><au>Reis, Rengin</au><au>Sipahi, Hande</au><au>Uba, Abdullahi Ibrahim</au><au>Gorobets, Mykola Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pronounced Anti‐Inflammatory and Analgesic Activities of a Spirofuran‐Triazolo[1,5‐a]pyrimidine Scaffold Available via Biginelli Multicomponent Condensation</atitle><jtitle>ChemistrySelect (Weinheim)</jtitle><date>2024-09-25</date><risdate>2024</risdate><volume>9</volume><issue>36</issue><epage>n/a</epage><issn>2365-6549</issn><eissn>2365-6549</eissn><abstract>In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT assay. Then, those with cell viability higher than 70 % were tested for their anti‐inflammatory activity at their non‐toxic doses by evaluating the nitrite level of the cell supernatants with the Griess reagent. Compounds 5 b, 5 d, 5 e, and 5 g demonstrated significant inhibition of nitrite production by 49 %, 59 %, 63 % respectively at 100 μM (p<0.05), whereas 56 % inhibition was seen with 50 μM of 5 g. According to the inhibition of PGE2, compound 5 b showed the most notable effect compared to control. All tested compounds, particularly 5 b, 5 d, 5 e and 5 f reduced the PGE2 level and showed potential analgesic activity. Seven heterocycles 5 a–g showed moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of 5 a–i with COX‐1. Instead, the modelling results also show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2. However, the simulation distinguished the key role of the 2‐OH group in stabilizing the inhibitor‐target complex only in the case of binding to COX‐2.
A series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) are evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. Compounds 5 a–g show moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of compounds 5 a–i with COX‐1. Instead, the modelling results show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2.</abstract><doi>10.1002/slct.202402286</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8089-4646</orcidid><orcidid>https://orcid.org/0000-0002-3484-2201</orcidid><orcidid>https://orcid.org/0000-0001-6373-5221</orcidid><orcidid>https://orcid.org/0000-0001-6482-3143</orcidid><orcidid>https://orcid.org/0000-0003-4949-1747</orcidid><orcidid>https://orcid.org/0000-0002-0853-108X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2365-6549 |
| ispartof | ChemistrySelect (Weinheim), 2024-09, Vol.9 (36), p.n/a |
| issn | 2365-6549 2365-6549 |
| language | eng |
| recordid | cdi_crossref_primary_10_1002_slct_202402286 |
| source | Access via Wiley Online Library |
| subjects | Anti-inflammatory activity Biginelli reaction Molecular docking MTT assay PGE2 |
| title | Pronounced Anti‐Inflammatory and Analgesic Activities of a Spirofuran‐Triazolo[1,5‐a]pyrimidine Scaffold Available via Biginelli Multicomponent Condensation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-07T09%3A47%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pronounced%20Anti%E2%80%90Inflammatory%20and%20Analgesic%20Activities%20of%20a%20Spirofuran%E2%80%90Triazolo%5B1,5%E2%80%90a%5Dpyrimidine%20Scaffold%20Available%20via%20Biginelli%20Multicomponent%20Condensation&rft.jtitle=ChemistrySelect%20(Weinheim)&rft.au=G%C3%BCm%C3%BC%C5%9F,%20Mustafa%20Kemal&rft.date=2024-09-25&rft.volume=9&rft.issue=36&rft.epage=n/a&rft.issn=2365-6549&rft.eissn=2365-6549&rft_id=info:doi/10.1002/slct.202402286&rft_dat=%3Cwiley_cross%3ESLCT202402286%3C/wiley_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |