Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis
Phospholipase A2 (PLA 2 ) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA 2 is considered to be one of the efficient methods to control inflammation. In silico docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA...
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| Veröffentlicht in: | Journal of molecular modeling 2013-04, Vol.19 (4), p.1811-1817 |
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| creator | Dileep, Kalarickal Vijayan Remya, Chandran Tintu, Ignatius Haridas, Madathilkovilakathu Sadasivan, Chittalakkottu |
| description | Phospholipase A2 (PLA
2
) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA
2
is considered to be one of the efficient methods to control inflammation.
In silico
docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA
2
(ppsPLA
2
) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies.
In silico
analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA
2
(hnpsPLA
2
) was determined using molecular docking studies. In order to corroborate the
in silico
results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA
2
. From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.
Figure
Inhibitory activity of IAA and IBA against PLA
2 |
| doi_str_mv | 10.1007/s00894-012-1741-4 |
| format | Article |
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2
) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA
2
is considered to be one of the efficient methods to control inflammation.
In silico
docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA
2
(ppsPLA
2
) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies.
In silico
analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA
2
(hnpsPLA
2
) was determined using molecular docking studies. In order to corroborate the
in silico
results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA
2
. From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.
Figure
Inhibitory activity of IAA and IBA against PLA
2</description><identifier>ISSN: 1610-2940</identifier><identifier>EISSN: 0948-5023</identifier><identifier>DOI: 10.1007/s00894-012-1741-4</identifier><identifier>PMID: 23315198</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Anti-Inflammatory Agents - chemistry ; Binding Sites ; Characterization and Evaluation of Materials ; Chemistry ; Chemistry and Materials Science ; Computer Appl. in Life Sciences ; Computer Applications in Chemistry ; Enzyme Inhibitors - chemistry ; Humans ; Indoleacetic Acids - chemistry ; Indoles - chemistry ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - chemistry ; Kinetics ; Molecular Docking Simulation ; Molecular Medicine ; Original Paper ; Pancreas - chemistry ; Pancreas - enzymology ; Phospholipase A2 Inhibitors ; Phospholipases A2 - chemistry ; Protein Binding ; Swine ; Theoretical and Computational Chemistry ; Thermodynamics</subject><ispartof>Journal of molecular modeling, 2013-04, Vol.19 (4), p.1811-1817</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1894-a1ae548be32398530900800c9cfc9f58022fea81bf106f7b41062449483daa6c3</citedby><cites>FETCH-LOGICAL-c1894-a1ae548be32398530900800c9cfc9f58022fea81bf106f7b41062449483daa6c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00894-012-1741-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00894-012-1741-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23315198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dileep, Kalarickal Vijayan</creatorcontrib><creatorcontrib>Remya, Chandran</creatorcontrib><creatorcontrib>Tintu, Ignatius</creatorcontrib><creatorcontrib>Haridas, Madathilkovilakathu</creatorcontrib><creatorcontrib>Sadasivan, Chittalakkottu</creatorcontrib><title>Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis</title><title>Journal of molecular modeling</title><addtitle>J Mol Model</addtitle><addtitle>J Mol Model</addtitle><description>Phospholipase A2 (PLA
2
) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA
2
is considered to be one of the efficient methods to control inflammation.
In silico
docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA
2
(ppsPLA
2
) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies.
In silico
analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA
2
(hnpsPLA
2
) was determined using molecular docking studies. In order to corroborate the
in silico
results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA
2
. From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.
Figure
Inhibitory activity of IAA and IBA against PLA
2</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Binding Sites</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Computer Appl. in Life Sciences</subject><subject>Computer Applications in Chemistry</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Humans</subject><subject>Indoleacetic Acids - chemistry</subject><subject>Indoles - chemistry</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - chemistry</subject><subject>Kinetics</subject><subject>Molecular Docking Simulation</subject><subject>Molecular Medicine</subject><subject>Original Paper</subject><subject>Pancreas - chemistry</subject><subject>Pancreas - enzymology</subject><subject>Phospholipase A2 Inhibitors</subject><subject>Phospholipases A2 - chemistry</subject><subject>Protein Binding</subject><subject>Swine</subject><subject>Theoretical and Computational Chemistry</subject><subject>Thermodynamics</subject><issn>1610-2940</issn><issn>0948-5023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFO3DAQhq2qqKyAB-BS-dhLYMZ2sjE3hApFQuqlnC3HmYBRNt56slvx9jha6JGDNbLm-0f6PyHOES4QYH3JAK01FaCqcG2wMl_ECqxpqxqU_ipW2CBUyho4FmfMLwCFrJtaqW_iWGmNNdp2Jbr7aabswxzTxDINkmmkMFMv49SnkWRPOe79HPfE8l-cn-X2OXF5Y9x6JnmtrgopOY4xJOmnJSf3cc7Lx4-vHPlUHA1-ZDp7nyfi8fbnn5tf1cPvu_ub64cq4FLEo6fatB1ppW1ba7ClIECwYQh2qFtQaiDfYjcgNMO6M2UoY0pj3XvfBH0ifhzubnP6uyOe3SZyoHH0E6UdO9RosSkKmoLiAQ05MWca3DbHjc-vDsEtdt3BrivO3GLXmZL5_n5-122o_5_4cFkAdQC4rKYnyu4l7XKRwJ9cfQP4fYRc</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Dileep, Kalarickal Vijayan</creator><creator>Remya, Chandran</creator><creator>Tintu, Ignatius</creator><creator>Haridas, Madathilkovilakathu</creator><creator>Sadasivan, Chittalakkottu</creator><general>Springer-Verlag</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></search><sort><creationdate>201304</creationdate><title>Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis</title><author>Dileep, Kalarickal Vijayan ; Remya, Chandran ; Tintu, Ignatius ; Haridas, Madathilkovilakathu ; Sadasivan, Chittalakkottu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1894-a1ae548be32398530900800c9cfc9f58022fea81bf106f7b41062449483daa6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Binding Sites</topic><topic>Characterization and Evaluation of Materials</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Computer Appl. in Life Sciences</topic><topic>Computer Applications in Chemistry</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Humans</topic><topic>Indoleacetic Acids - chemistry</topic><topic>Indoles - chemistry</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - chemistry</topic><topic>Kinetics</topic><topic>Molecular Docking Simulation</topic><topic>Molecular Medicine</topic><topic>Original Paper</topic><topic>Pancreas - chemistry</topic><topic>Pancreas - enzymology</topic><topic>Phospholipase A2 Inhibitors</topic><topic>Phospholipases A2 - chemistry</topic><topic>Protein Binding</topic><topic>Swine</topic><topic>Theoretical and Computational Chemistry</topic><topic>Thermodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dileep, Kalarickal Vijayan</creatorcontrib><creatorcontrib>Remya, Chandran</creatorcontrib><creatorcontrib>Tintu, Ignatius</creatorcontrib><creatorcontrib>Haridas, Madathilkovilakathu</creatorcontrib><creatorcontrib>Sadasivan, Chittalakkottu</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>Journal of molecular modeling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dileep, Kalarickal Vijayan</au><au>Remya, Chandran</au><au>Tintu, Ignatius</au><au>Haridas, Madathilkovilakathu</au><au>Sadasivan, Chittalakkottu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis</atitle><jtitle>Journal of molecular modeling</jtitle><stitle>J Mol Model</stitle><addtitle>J Mol Model</addtitle><date>2013-04</date><risdate>2013</risdate><volume>19</volume><issue>4</issue><spage>1811</spage><epage>1817</epage><pages>1811-1817</pages><issn>1610-2940</issn><eissn>0948-5023</eissn><abstract>Phospholipase A2 (PLA
2
) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA
2
is considered to be one of the efficient methods to control inflammation.
In silico
docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA
2
(ppsPLA
2
) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies.
In silico
analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA
2
(hnpsPLA
2
) was determined using molecular docking studies. In order to corroborate the
in silico
results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA
2
. From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.
Figure
Inhibitory activity of IAA and IBA against PLA
2</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>23315198</pmid><doi>10.1007/s00894-012-1741-4</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - chemistry Binding Sites Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Computer Appl. in Life Sciences Computer Applications in Chemistry Enzyme Inhibitors - chemistry Humans Indoleacetic Acids - chemistry Indoles - chemistry Isoenzymes - antagonists & inhibitors Isoenzymes - chemistry Kinetics Molecular Docking Simulation Molecular Medicine Original Paper Pancreas - chemistry Pancreas - enzymology Phospholipase A2 Inhibitors Phospholipases A2 - chemistry Protein Binding Swine Theoretical and Computational Chemistry Thermodynamics |
| title | Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis |
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