Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR
Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclizati...
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| Veröffentlicht in: | European journal of medicinal chemistry 2016-08, Vol.118, p.250-258 |
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| creator | Abdelall, Eman K.A. Kamel, Gehan M. |
| description | Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM).
[Display omitted]
•New thiazolo-celecoxib analogues were designed and synthesized.•Thiazolo-celecoxib drug hybrid showed higher COX-2/15-LOX inhibition properties.•Designed compounds were evaluated as anti-inflammatory activity using Carrageenan-induced rat paw edema and proved activity.•Ulcer liability index of compounds was determined and they showed higher safety profiles.•Most of the compounds were effective as anti-inflammatory and more selective towards COX-2/15-LOX. |
| doi_str_mv | 10.1016/j.ejmech.2016.04.049 |
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[Display omitted]
•New thiazolo-celecoxib analogues were designed and synthesized.•Thiazolo-celecoxib drug hybrid showed higher COX-2/15-LOX inhibition properties.•Designed compounds were evaluated as anti-inflammatory activity using Carrageenan-induced rat paw edema and proved activity.•Ulcer liability index of compounds was determined and they showed higher safety profiles.•Most of the compounds were effective as anti-inflammatory and more selective towards COX-2/15-LOX.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2016.04.049</identifier><identifier>PMID: 27131067</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>15-Lipoxygenase inhibitors ; Animals ; Anti-inflammatory ; Anti-Inflammatory Agents, Non-Steroidal - adverse effects ; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis ; Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Arachidonate 15-Lipoxygenase - metabolism ; Cattle ; Celecoxib - adverse effects ; Celecoxib - chemical synthesis ; Celecoxib - chemistry ; Celecoxib - pharmacology ; Celecoxib analogues ; Chemistry Techniques, Synthetic ; Cyclization ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase 2 Inhibitors - adverse effects ; Cyclooxygenase 2 Inhibitors - chemical synthesis ; Cyclooxygenase 2 Inhibitors - chemistry ; Cyclooxygenase 2 Inhibitors - pharmacology ; Cyclooxygenase inhibitors ; DMFDMA ; Ethyl trifloroacetate ; Lipoxygenase Inhibitors - adverse effects ; Lipoxygenase Inhibitors - chemical synthesis ; Lipoxygenase Inhibitors - chemistry ; Lipoxygenase Inhibitors - pharmacology ; Magnetic Resonance Spectroscopy ; Male ; Pyrazoles - chemistry ; Rats ; SO2NH2 pharmacophores ; Stereoisomerism ; Thiazoles - chemistry ; Ulcer - chemically induced</subject><ispartof>European journal of medicinal chemistry, 2016-08, Vol.118, p.250-258</ispartof><rights>2016 Elsevier Masson SAS</rights><rights>Copyright © 2016 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-23b79fe22dcfdb82cedcd8b3873d6a749c99aa9aec597e5fb20152bd87f88d5b3</citedby><cites>FETCH-LOGICAL-c362t-23b79fe22dcfdb82cedcd8b3873d6a749c99aa9aec597e5fb20152bd87f88d5b3</cites><orcidid>0000-0001-6075-3563</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2016.04.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27131067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abdelall, Eman K.A.</creatorcontrib><creatorcontrib>Kamel, Gehan M.</creatorcontrib><title>Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM).
[Display omitted]
•New thiazolo-celecoxib analogues were designed and synthesized.•Thiazolo-celecoxib drug hybrid showed higher COX-2/15-LOX inhibition properties.•Designed compounds were evaluated as anti-inflammatory activity using Carrageenan-induced rat paw edema and proved activity.•Ulcer liability index of compounds was determined and they showed higher safety profiles.•Most of the compounds were effective as anti-inflammatory and more selective towards COX-2/15-LOX.</description><subject>15-Lipoxygenase inhibitors</subject><subject>Animals</subject><subject>Anti-inflammatory</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Arachidonate 15-Lipoxygenase - metabolism</subject><subject>Cattle</subject><subject>Celecoxib - adverse effects</subject><subject>Celecoxib - chemical synthesis</subject><subject>Celecoxib - chemistry</subject><subject>Celecoxib - pharmacology</subject><subject>Celecoxib analogues</subject><subject>Chemistry Techniques, Synthetic</subject><subject>Cyclization</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase 2 Inhibitors - adverse effects</subject><subject>Cyclooxygenase 2 Inhibitors - chemical synthesis</subject><subject>Cyclooxygenase 2 Inhibitors - chemistry</subject><subject>Cyclooxygenase 2 Inhibitors - pharmacology</subject><subject>Cyclooxygenase inhibitors</subject><subject>DMFDMA</subject><subject>Ethyl trifloroacetate</subject><subject>Lipoxygenase Inhibitors - adverse effects</subject><subject>Lipoxygenase Inhibitors - chemical synthesis</subject><subject>Lipoxygenase Inhibitors - chemistry</subject><subject>Lipoxygenase Inhibitors - pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Pyrazoles - chemistry</subject><subject>Rats</subject><subject>SO2NH2 pharmacophores</subject><subject>Stereoisomerism</subject><subject>Thiazoles - chemistry</subject><subject>Ulcer - chemically induced</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu1DAUtRCIDgN_gJCXbDJ17CSOWSChlpdUQOKxtvy4nvEosQc7U5r-Ej-Jh5Quka5k-eo8dO5B6HlNNjWpu_P9BvYjmN2Glt-GNGXEA7SqeddXjLbNQ7QilLKqpaw5Q09y3hNC2o6Qx-iM8prVpOMr9PvbHKYdZJ9xdDjALzztvLqNQ6wMDGDijddYBTXE7REyVhnboxqwmc0Q4828haAyVPS8bqvBH-432Ied136KKb_ClzBBGn1Qk4_hZJNg62OVD2C88wZb7xwkCBM-zOnkDX_1_e1C0DOml_jzp69P0SOnhgzP7t41-vHu7feLD9XVl_cfL95cVYZ1dKoo01w4oNQaZ3VPDVhje816zmyneCOMEEoJBaYVHFqnywFbqm3PXd_bVrM1ernoHlL8WVJPcvS5XGNQAeIxy5oLJggXRXCNmgVqUsw5gZOH5EeVZlkTeapJ7uVSkzzVJElTRhTaizuHox7B3pP-9VIArxcAlJzXHpLMxkMoUXwCM0kb_f8d_gAISKqJ</recordid><startdate>20160808</startdate><enddate>20160808</enddate><creator>Abdelall, Eman K.A.</creator><creator>Kamel, Gehan M.</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6075-3563</orcidid></search><sort><creationdate>20160808</creationdate><title>Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR</title><author>Abdelall, Eman K.A. ; Kamel, Gehan M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-23b79fe22dcfdb82cedcd8b3873d6a749c99aa9aec597e5fb20152bd87f88d5b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>15-Lipoxygenase inhibitors</topic><topic>Animals</topic><topic>Anti-inflammatory</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Arachidonate 15-Lipoxygenase - metabolism</topic><topic>Cattle</topic><topic>Celecoxib - adverse effects</topic><topic>Celecoxib - chemical synthesis</topic><topic>Celecoxib - chemistry</topic><topic>Celecoxib - pharmacology</topic><topic>Celecoxib analogues</topic><topic>Chemistry Techniques, Synthetic</topic><topic>Cyclization</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase 2 Inhibitors - adverse effects</topic><topic>Cyclooxygenase 2 Inhibitors - chemical synthesis</topic><topic>Cyclooxygenase 2 Inhibitors - chemistry</topic><topic>Cyclooxygenase 2 Inhibitors - pharmacology</topic><topic>Cyclooxygenase inhibitors</topic><topic>DMFDMA</topic><topic>Ethyl trifloroacetate</topic><topic>Lipoxygenase Inhibitors - adverse effects</topic><topic>Lipoxygenase Inhibitors - chemical synthesis</topic><topic>Lipoxygenase Inhibitors - chemistry</topic><topic>Lipoxygenase Inhibitors - pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Pyrazoles - chemistry</topic><topic>Rats</topic><topic>SO2NH2 pharmacophores</topic><topic>Stereoisomerism</topic><topic>Thiazoles - chemistry</topic><topic>Ulcer - chemically induced</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abdelall, Eman K.A.</creatorcontrib><creatorcontrib>Kamel, Gehan M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abdelall, Eman K.A.</au><au>Kamel, Gehan M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2016-08-08</date><risdate>2016</risdate><volume>118</volume><spage>250</spage><epage>258</epage><pages>250-258</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><abstract>Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM).
[Display omitted]
•New thiazolo-celecoxib analogues were designed and synthesized.•Thiazolo-celecoxib drug hybrid showed higher COX-2/15-LOX inhibition properties.•Designed compounds were evaluated as anti-inflammatory activity using Carrageenan-induced rat paw edema and proved activity.•Ulcer liability index of compounds was determined and they showed higher safety profiles.•Most of the compounds were effective as anti-inflammatory and more selective towards COX-2/15-LOX.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>27131067</pmid><doi>10.1016/j.ejmech.2016.04.049</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-6075-3563</orcidid></addata></record> |
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| ispartof | European journal of medicinal chemistry, 2016-08, Vol.118, p.250-258 |
| issn | 0223-5234 1768-3254 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 15-Lipoxygenase inhibitors Animals Anti-inflammatory Anti-Inflammatory Agents, Non-Steroidal - adverse effects Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis Anti-Inflammatory Agents, Non-Steroidal - chemistry Anti-Inflammatory Agents, Non-Steroidal - pharmacology Arachidonate 15-Lipoxygenase - metabolism Cattle Celecoxib - adverse effects Celecoxib - chemical synthesis Celecoxib - chemistry Celecoxib - pharmacology Celecoxib analogues Chemistry Techniques, Synthetic Cyclization Cyclooxygenase 2 - metabolism Cyclooxygenase 2 Inhibitors - adverse effects Cyclooxygenase 2 Inhibitors - chemical synthesis Cyclooxygenase 2 Inhibitors - chemistry Cyclooxygenase 2 Inhibitors - pharmacology Cyclooxygenase inhibitors DMFDMA Ethyl trifloroacetate Lipoxygenase Inhibitors - adverse effects Lipoxygenase Inhibitors - chemical synthesis Lipoxygenase Inhibitors - chemistry Lipoxygenase Inhibitors - pharmacology Magnetic Resonance Spectroscopy Male Pyrazoles - chemistry Rats SO2NH2 pharmacophores Stereoisomerism Thiazoles - chemistry Ulcer - chemically induced |
| title | Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR |
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