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Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat
Recently, some PPARγ agonists like pioglitazone, rosiglitazone, and other newer thiazolidine‐2, 4‐dione (TZD) derivatives have been shown to be neuroprotective in experimental model of cerebral ischemia/reperfusion (I/R) injury. Replacement of active pharmacophore viz: thiazolidine‐2,4‐dione of thes...
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| Published in: | Chemical biology & drug design 2011-09, Vol.78 (3), p.445-453 |
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| Main Authors: | , , , , , |
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| cites | cdi_FETCH-LOGICAL-c4403-92667dd8f1dfb0fb92e8c19d096f05e58d77a334578f5fd5f5bb8075f17d4d7a3 |
| container_end_page | 453 |
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| container_title | Chemical biology & drug design |
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| creator | Raghubir, Ram Verma, Rajkumar Samuel, Sheeba S. Raza, Saman Haq, Wajahul Katti, Seturam B. |
| description | Recently, some PPARγ agonists like pioglitazone, rosiglitazone, and other newer thiazolidine‐2, 4‐dione (TZD) derivatives have been shown to be neuroprotective in experimental model of cerebral ischemia/reperfusion (I/R) injury. Replacement of active pharmacophore viz: thiazolidine‐2,4‐dione of these PPARγ agonists with biologically privileged scaffold thiazolidin‐4‐one derivatives have been synthesized and bioevaluated in focal cerebral ischemia model in rats with an aim to ameliorate cerebral ischemic damage. Of 20 synthesized molecules, three of the substituted compounds (2, 6 and 18) have shown significant (p |
| doi_str_mv | 10.1111/j.1747-0285.2011.01153.x |
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The newly developed thiazolidine‐4‐one derivatives were synthesized and screened for their anti‐stroke activity. These derivatives may provide a new pharmacophore for the development of a new class of potent anti‐stroke agents.</description><identifier>ISSN: 1747-0277</identifier><identifier>EISSN: 1747-0285</identifier><identifier>DOI: 10.1111/j.1747-0285.2011.01153.x</identifier><identifier>PMID: 21649861</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animal models ; Animals ; Brain - drug effects ; Brain - pathology ; Brain Ischemia - drug therapy ; Brain Ischemia - pathology ; cerebral ischemia ; Drug development ; Excitatory Amino Acid Transporter 2 - metabolism ; Glutamic acid ; Glutamic Acid - metabolism ; Glutathione - metabolism ; Injuries ; Ischemia ; Male ; Neuroprotection ; Neuroprotective Agents - chemical synthesis ; Neuroprotective Agents - chemistry ; Neuroprotective Agents - therapeutic use ; Peroxisome proliferator-activated receptors ; pharmacophores ; pioglitazone ; PPAR gamma - agonists ; PPAR gamma - metabolism ; PPARγ agonist ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; rosiglitazone ; scaffolds ; thiazolidin-4-one ; Thiazolidinediones - chemical synthesis ; Thiazolidinediones - chemistry ; Thiazolidinediones - therapeutic use</subject><ispartof>Chemical biology & drug design, 2011-09, Vol.78 (3), p.445-453</ispartof><rights>2011 John Wiley & Sons A/S</rights><rights>2011 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4403-92667dd8f1dfb0fb92e8c19d096f05e58d77a334578f5fd5f5bb8075f17d4d7a3</citedby><cites>FETCH-LOGICAL-c4403-92667dd8f1dfb0fb92e8c19d096f05e58d77a334578f5fd5f5bb8075f17d4d7a3</cites></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/21649861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raghubir, Ram</creatorcontrib><creatorcontrib>Verma, Rajkumar</creatorcontrib><creatorcontrib>Samuel, Sheeba S.</creatorcontrib><creatorcontrib>Raza, Saman</creatorcontrib><creatorcontrib>Haq, Wajahul</creatorcontrib><creatorcontrib>Katti, Seturam B.</creatorcontrib><title>Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat</title><title>Chemical biology & drug design</title><addtitle>Chem Biol Drug Des</addtitle><description>Recently, some PPARγ agonists like pioglitazone, rosiglitazone, and other newer thiazolidine‐2, 4‐dione (TZD) derivatives have been shown to be neuroprotective in experimental model of cerebral ischemia/reperfusion (I/R) injury. Replacement of active pharmacophore viz: thiazolidine‐2,4‐dione of these PPARγ agonists with biologically privileged scaffold thiazolidin‐4‐one derivatives have been synthesized and bioevaluated in focal cerebral ischemia model in rats with an aim to ameliorate cerebral ischemic damage. Of 20 synthesized molecules, three of the substituted compounds (2, 6 and 18) have shown significant (p < 0.001) neuroprotection even much better than rosiglitazone at same dose, when administered 1 h prior to 2/24hrI/R cerebral injury in rats, whereas compounds 10, 15, and 17 also showed significant but moderate effect on most of the parameters used in the study. Moreover, compound 2 and 6 also showed curative potential after 6 h post I/R treatment. The compound 2 has also shown significant effect on glutamate uptake by perhaps enhancing the GLT‐1 activity. Thus, the present study indicates that some of the synthesized thiazolidin‐4‐one substituted PPARγ agonists exhibit better neuroprotection and have potential to ameliorate the ischemic damage. Therefore, this novel class of compounds could be further suitably modified to obtain potent anti‐ischemic agents, warranting clinical exploitation.
The newly developed thiazolidine‐4‐one derivatives were synthesized and screened for their anti‐stroke activity. These derivatives may provide a new pharmacophore for the development of a new class of potent anti‐stroke agents.</description><subject>Animal models</subject><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - pathology</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - pathology</subject><subject>cerebral ischemia</subject><subject>Drug development</subject><subject>Excitatory Amino Acid Transporter 2 - metabolism</subject><subject>Glutamic acid</subject><subject>Glutamic Acid - metabolism</subject><subject>Glutathione - metabolism</subject><subject>Injuries</subject><subject>Ischemia</subject><subject>Male</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - chemical synthesis</subject><subject>Neuroprotective Agents - chemistry</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>pharmacophores</subject><subject>pioglitazone</subject><subject>PPAR gamma - agonists</subject><subject>PPAR gamma - metabolism</subject><subject>PPARγ agonist</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reperfusion</subject><subject>rosiglitazone</subject><subject>scaffolds</subject><subject>thiazolidin-4-one</subject><subject>Thiazolidinediones - chemical synthesis</subject><subject>Thiazolidinediones - chemistry</subject><subject>Thiazolidinediones - therapeutic use</subject><issn>1747-0277</issn><issn>1747-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqNkV9rFDEUxYMotla_guRNX2ZMMskk8yLUXXctrNY_FUGEkJnc0GxnJ20yW7d-ejNu3UcxEHLg_u4JnIMQpqSk-bxal1RyWRCmRMkIpWW-oip3D9DxYfDwoKU8Qk9SWhPCuWDqMTpitOaNqukx-nE6jL74MsZwBfhjDM73gIPDF5fe_Aq9t34oeHE-AJ5D9Ldm9LeQsB_wInSmxzOI0MYszlJ3CRtv8PtgoZ-Az2Z8ih450yd4dv-eoK-Ltxezd8XqfHk2O10VHeekKhpW19Ja5ah1LXFtw0B1tLGkqR0RIJSV0lQVF1I54axwom0VkcJRabnNoxP0Yu97HcPNFtKoNz510PdmgLBNWqmqoqTmPJMv_0lSxijlVNUso2qPdjGkFMHp6-g3Jt5pSvTUgl7rKWA9ha2nFvSfFvQurz6__2XbbsAeFv_GnoHXe-Bnjvvuv4317M18PslsUOwNfBphdzAw8UrXspJCf_uw1HP6fUnI6pNeVL8BETGjcw</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Raghubir, Ram</creator><creator>Verma, Rajkumar</creator><creator>Samuel, Sheeba S.</creator><creator>Raza, Saman</creator><creator>Haq, Wajahul</creator><creator>Katti, Seturam B.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7T7</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201109</creationdate><title>Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat</title><author>Raghubir, Ram ; Verma, Rajkumar ; Samuel, Sheeba S. ; Raza, Saman ; Haq, Wajahul ; Katti, Seturam B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4403-92667dd8f1dfb0fb92e8c19d096f05e58d77a334578f5fd5f5bb8075f17d4d7a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Brain - drug effects</topic><topic>Brain - pathology</topic><topic>Brain Ischemia - drug therapy</topic><topic>Brain Ischemia - pathology</topic><topic>cerebral ischemia</topic><topic>Drug development</topic><topic>Excitatory Amino Acid Transporter 2 - metabolism</topic><topic>Glutamic acid</topic><topic>Glutamic Acid - metabolism</topic><topic>Glutathione - metabolism</topic><topic>Injuries</topic><topic>Ischemia</topic><topic>Male</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - chemical synthesis</topic><topic>Neuroprotective Agents - chemistry</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>pharmacophores</topic><topic>pioglitazone</topic><topic>PPAR gamma - agonists</topic><topic>PPAR gamma - metabolism</topic><topic>PPARγ agonist</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reperfusion</topic><topic>rosiglitazone</topic><topic>scaffolds</topic><topic>thiazolidin-4-one</topic><topic>Thiazolidinediones - chemical synthesis</topic><topic>Thiazolidinediones - chemistry</topic><topic>Thiazolidinediones - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raghubir, Ram</creatorcontrib><creatorcontrib>Verma, Rajkumar</creatorcontrib><creatorcontrib>Samuel, Sheeba S.</creatorcontrib><creatorcontrib>Raza, Saman</creatorcontrib><creatorcontrib>Haq, Wajahul</creatorcontrib><creatorcontrib>Katti, Seturam B.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical biology & drug design</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raghubir, Ram</au><au>Verma, Rajkumar</au><au>Samuel, Sheeba S.</au><au>Raza, Saman</au><au>Haq, Wajahul</au><au>Katti, Seturam B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat</atitle><jtitle>Chemical biology & drug design</jtitle><addtitle>Chem Biol Drug Des</addtitle><date>2011-09</date><risdate>2011</risdate><volume>78</volume><issue>3</issue><spage>445</spage><epage>453</epage><pages>445-453</pages><issn>1747-0277</issn><eissn>1747-0285</eissn><abstract>Recently, some PPARγ agonists like pioglitazone, rosiglitazone, and other newer thiazolidine‐2, 4‐dione (TZD) derivatives have been shown to be neuroprotective in experimental model of cerebral ischemia/reperfusion (I/R) injury. Replacement of active pharmacophore viz: thiazolidine‐2,4‐dione of these PPARγ agonists with biologically privileged scaffold thiazolidin‐4‐one derivatives have been synthesized and bioevaluated in focal cerebral ischemia model in rats with an aim to ameliorate cerebral ischemic damage. Of 20 synthesized molecules, three of the substituted compounds (2, 6 and 18) have shown significant (p < 0.001) neuroprotection even much better than rosiglitazone at same dose, when administered 1 h prior to 2/24hrI/R cerebral injury in rats, whereas compounds 10, 15, and 17 also showed significant but moderate effect on most of the parameters used in the study. Moreover, compound 2 and 6 also showed curative potential after 6 h post I/R treatment. The compound 2 has also shown significant effect on glutamate uptake by perhaps enhancing the GLT‐1 activity. Thus, the present study indicates that some of the synthesized thiazolidin‐4‐one substituted PPARγ agonists exhibit better neuroprotection and have potential to ameliorate the ischemic damage. Therefore, this novel class of compounds could be further suitably modified to obtain potent anti‐ischemic agents, warranting clinical exploitation.
The newly developed thiazolidine‐4‐one derivatives were synthesized and screened for their anti‐stroke activity. These derivatives may provide a new pharmacophore for the development of a new class of potent anti‐stroke agents.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21649861</pmid><doi>10.1111/j.1747-0285.2011.01153.x</doi><tpages>9</tpages></addata></record> |
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| ispartof | Chemical biology & drug design, 2011-09, Vol.78 (3), p.445-453 |
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| subjects | Animal models Animals Brain - drug effects Brain - pathology Brain Ischemia - drug therapy Brain Ischemia - pathology cerebral ischemia Drug development Excitatory Amino Acid Transporter 2 - metabolism Glutamic acid Glutamic Acid - metabolism Glutathione - metabolism Injuries Ischemia Male Neuroprotection Neuroprotective Agents - chemical synthesis Neuroprotective Agents - chemistry Neuroprotective Agents - therapeutic use Peroxisome proliferator-activated receptors pharmacophores pioglitazone PPAR gamma - agonists PPAR gamma - metabolism PPARγ agonist Rats Rats, Sprague-Dawley Reperfusion rosiglitazone scaffolds thiazolidin-4-one Thiazolidinediones - chemical synthesis Thiazolidinediones - chemistry Thiazolidinediones - therapeutic use |
| title | Anti-Stroke Profile of Thiazolidin-4-One Derivatives in Focal Cerebral Ischemia Model in Rat |
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