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Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors
A series of novel indole-thiazolidinedione hybrid analogues ( to ) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues, was found to be the most active PL inhibitor with an IC of 2.67 µM. Furthermore, enzyme inhibition k...
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| Published in: | Journal of biomolecular structure & dynamics 2023-12, p.1-20 |
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| Main Authors: | , , , , |
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| Language: | English |
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| container_title | Journal of biomolecular structure & dynamics |
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| creator | George, Ginson Auti, Prashant S Sengupta, Pracheta Yadav, Nisha Paul, Atish T |
| description | A series of novel indole-thiazolidinedione hybrid analogues (
to
) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues,
was found to be the most active PL inhibitor with an IC
of 2.67 µM. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed
fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the
results (Pearson's
= 0.8355,
|
| doi_str_mv | 10.1080/07391102.2023.2293255 |
| format | article |
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to
) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues,
was found to be the most active PL inhibitor with an IC
of 2.67 µM. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed
fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the
results (Pearson's
= 0.8355,
< 0.05). A molecular dynamics study (100 ns) indicated that
was stable in a dynamic environment. The analogue
exhibited potential antioxidant activity and was devoid of cytotoxic effect on RAW 264.7 cells. Based on the
profiles,
was selected for the
pharmacological evaluation. Oral triglyceride tolerance test highlighted effect of
on the inhibition of triglyceride absorption. A four-week treatment of
in the HFD feed mice provided information regarding its anti-obesity effect with respect to parameters such as body weight, triglycerides, total cholesterol and high-density lipids. Quantification of the faecal triglyceride contents inveterates the potential role of
in the PL inhibition. Overall, the synthesized analogue
exerted an anti-obesity effect comparable to orlistat. All these results demonstrated the potential role of the newly synthesised indole-thiazolidinedione hybrid analogues in PL inhibition and may be studied further to find potential drug candidates for treating obesity.Communicated by Ramaswamy H. Sarma.</description><identifier>ISSN: 0739-1102</identifier><identifier>EISSN: 1538-0254</identifier><identifier>DOI: 10.1080/07391102.2023.2293255</identifier><identifier>PMID: 38095559</identifier><language>eng</language><publisher>England</publisher><ispartof>Journal of biomolecular structure & dynamics, 2023-12, p.1-20</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c309t-25253420453264874b5607848b1529948955a25abd2a66d8ff86108d627d633d3</citedby><cites>FETCH-LOGICAL-c309t-25253420453264874b5607848b1529948955a25abd2a66d8ff86108d627d633d3</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/38095559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>George, Ginson</creatorcontrib><creatorcontrib>Auti, Prashant S</creatorcontrib><creatorcontrib>Sengupta, Pracheta</creatorcontrib><creatorcontrib>Yadav, Nisha</creatorcontrib><creatorcontrib>Paul, Atish T</creatorcontrib><title>Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors</title><title>Journal of biomolecular structure & dynamics</title><addtitle>J Biomol Struct Dyn</addtitle><description>A series of novel indole-thiazolidinedione hybrid analogues (
to
) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues,
was found to be the most active PL inhibitor with an IC
of 2.67 µM. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed
fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the
results (Pearson's
= 0.8355,
< 0.05). A molecular dynamics study (100 ns) indicated that
was stable in a dynamic environment. The analogue
exhibited potential antioxidant activity and was devoid of cytotoxic effect on RAW 264.7 cells. Based on the
profiles,
was selected for the
pharmacological evaluation. Oral triglyceride tolerance test highlighted effect of
on the inhibition of triglyceride absorption. A four-week treatment of
in the HFD feed mice provided information regarding its anti-obesity effect with respect to parameters such as body weight, triglycerides, total cholesterol and high-density lipids. Quantification of the faecal triglyceride contents inveterates the potential role of
in the PL inhibition. Overall, the synthesized analogue
exerted an anti-obesity effect comparable to orlistat. All these results demonstrated the potential role of the newly synthesised indole-thiazolidinedione hybrid analogues in PL inhibition and may be studied further to find potential drug candidates for treating obesity.Communicated by Ramaswamy H. Sarma.</description><issn>0739-1102</issn><issn>1538-0254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNo9kc1u3CAURlHVqJkmfYRWLLuop3AxNiyrqH9SpCySrK1rg2MqDC7YkaZPk0cNo0y6gsX5Dtz7EfKRsz1nin1lrdCcM9gDA7EH0AKkfEN2XApVMZD1W7I7MtUROifvc_7DGHDe8nfkXCimpZR6R55uD2GdbHb5C52jt8PmMZWbsd678EAxGLpMmGYcoo8PbkBP7SP6DVcXA40jDfHReuqCKelqnRz-i94ZF6wpgKU9ZmvodOiTM8WGRbLZTDHTJa42rK4IFwxDssU4UO-WEii6yfVujSlfkrMRfbYfTucFuf_x_e7qV3V98_P31bfrahBMrxVIkKIGVksBTa3aupcNa1Wtei5B61qVeREk9gawaYwaR9WUPZoGWtMIYcQF-fziXVL8W364drPLQ9kCBhu33IFmoBvZirqg8gUdUsw52bFbkpsxHTrOumM53Ws53bGc7lROyX06PbH1szX_U69tiGfB5Iz5</recordid><startdate>20231214</startdate><enddate>20231214</enddate><creator>George, Ginson</creator><creator>Auti, Prashant S</creator><creator>Sengupta, Pracheta</creator><creator>Yadav, Nisha</creator><creator>Paul, Atish T</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20231214</creationdate><title>Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors</title><author>George, Ginson ; Auti, Prashant S ; Sengupta, Pracheta ; Yadav, Nisha ; Paul, Atish T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c309t-25253420453264874b5607848b1529948955a25abd2a66d8ff86108d627d633d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>George, Ginson</creatorcontrib><creatorcontrib>Auti, Prashant S</creatorcontrib><creatorcontrib>Sengupta, Pracheta</creatorcontrib><creatorcontrib>Yadav, Nisha</creatorcontrib><creatorcontrib>Paul, Atish T</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biomolecular structure & dynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>George, Ginson</au><au>Auti, Prashant S</au><au>Sengupta, Pracheta</au><au>Yadav, Nisha</au><au>Paul, Atish T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors</atitle><jtitle>Journal of biomolecular structure & dynamics</jtitle><addtitle>J Biomol Struct Dyn</addtitle><date>2023-12-14</date><risdate>2023</risdate><spage>1</spage><epage>20</epage><pages>1-20</pages><issn>0739-1102</issn><eissn>1538-0254</eissn><abstract>A series of novel indole-thiazolidinedione hybrid analogues (
to
) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues,
was found to be the most active PL inhibitor with an IC
of 2.67 µM. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed
fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the
results (Pearson's
= 0.8355,
< 0.05). A molecular dynamics study (100 ns) indicated that
was stable in a dynamic environment. The analogue
exhibited potential antioxidant activity and was devoid of cytotoxic effect on RAW 264.7 cells. Based on the
profiles,
was selected for the
pharmacological evaluation. Oral triglyceride tolerance test highlighted effect of
on the inhibition of triglyceride absorption. A four-week treatment of
in the HFD feed mice provided information regarding its anti-obesity effect with respect to parameters such as body weight, triglycerides, total cholesterol and high-density lipids. Quantification of the faecal triglyceride contents inveterates the potential role of
in the PL inhibition. Overall, the synthesized analogue
exerted an anti-obesity effect comparable to orlistat. All these results demonstrated the potential role of the newly synthesised indole-thiazolidinedione hybrid analogues in PL inhibition and may be studied further to find potential drug candidates for treating obesity.Communicated by Ramaswamy H. Sarma.</abstract><cop>England</cop><pmid>38095559</pmid><doi>10.1080/07391102.2023.2293255</doi><tpages>20</tpages></addata></record> |
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| source | Taylor and Francis Science and Technology Collection |
| title | Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors |
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