Anti-malarial drug targets: Screening for inhibitors of 2C-methyl- d-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants
The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in numerous pathogenic eubacteria and in apicoplast-type protozoa, most notably Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective ch...
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| Veröffentlicht in: | Phytomedicine (Stuttgart) 2007-04, Vol.14 (4), p.242-249 |
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| creator | Kaiser, J. Yassin, M. Prakash, S. Safi, N. Agami, M. Lauw, S. Ostrozhenkova, E. Bacher, A. Rohdich, F. Eisenreich, W. Safi, J. Golan-Goldhirsh, A. |
| description | The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in numerous pathogenic eubacteria and in apicoplast-type protozoa, most notably
Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective chemotherapy. The first committed step of the non-mevalonate pathway is catalyzed by 2C-methyl-
d-erythritol 4-phosphate synthase (IspC). Using photometric and NMR spectroscopic assays, we screened extracts of Mediterranean plants for inhibitors of the enzyme. Strongest inhibitory activity was found in leaf extracts of
Cercis siliquastrum. |
| doi_str_mv | 10.1016/j.phymed.2006.12.018 |
| format | Article |
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Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective chemotherapy. The first committed step of the non-mevalonate pathway is catalyzed by 2C-methyl-
d-erythritol 4-phosphate synthase (IspC). Using photometric and NMR spectroscopic assays, we screened extracts of Mediterranean plants for inhibitors of the enzyme. Strongest inhibitory activity was found in leaf extracts of
Cercis siliquastrum.</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2006.12.018</identifier><identifier>PMID: 17293098</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Aldose-Ketose Isomerases - antagonists & inhibitors ; Aldose-Ketose Isomerases - chemistry ; Amino Acid Sequence ; Animals ; Antibiotic ; Antimalarials ; Antimalarials - chemistry ; Cercis siliquastrum ; Deoxyxylulose inhibitors of 2C-methyl-D-erythritol 4-phosphate sythase (IspCprotein) ; Escherichia coli - enzymology ; Escherichia coli - genetics ; Health aspects ; Humans ; Malaria ; Malaria, Falciparum - drug therapy ; Medicinal plants ; Mediterranean Region ; Molecular Sequence Data ; Multienzyme Complexes - antagonists & inhibitors ; Multienzyme Complexes - chemistry ; Oxidoreductases - antagonists & inhibitors ; Oxidoreductases - chemistry ; Phytotherapy ; Plant Extracts - chemistry ; Plant Leaves ; Plants, Medicinal ; Plasmodium falciparum - enzymology ; Plasmodium falciparum - genetics ; Terpene ; Terpenes</subject><ispartof>Phytomedicine (Stuttgart), 2007-04, Vol.14 (4), p.242-249</ispartof><rights>2007 Elsevier GmbH</rights><rights>COPYRIGHT 2007 Urban & Fischer Verlag</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-3d595636531a64235eadd9232c37fbd57f7cf2498e7c4baec99df70e0e8ee4103</citedby><cites>FETCH-LOGICAL-c465t-3d595636531a64235eadd9232c37fbd57f7cf2498e7c4baec99df70e0e8ee4103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S094471130600225X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17293098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaiser, J.</creatorcontrib><creatorcontrib>Yassin, M.</creatorcontrib><creatorcontrib>Prakash, S.</creatorcontrib><creatorcontrib>Safi, N.</creatorcontrib><creatorcontrib>Agami, M.</creatorcontrib><creatorcontrib>Lauw, S.</creatorcontrib><creatorcontrib>Ostrozhenkova, E.</creatorcontrib><creatorcontrib>Bacher, A.</creatorcontrib><creatorcontrib>Rohdich, F.</creatorcontrib><creatorcontrib>Eisenreich, W.</creatorcontrib><creatorcontrib>Safi, J.</creatorcontrib><creatorcontrib>Golan-Goldhirsh, A.</creatorcontrib><title>Anti-malarial drug targets: Screening for inhibitors of 2C-methyl- d-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in numerous pathogenic eubacteria and in apicoplast-type protozoa, most notably
Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective chemotherapy. The first committed step of the non-mevalonate pathway is catalyzed by 2C-methyl-
d-erythritol 4-phosphate synthase (IspC). Using photometric and NMR spectroscopic assays, we screened extracts of Mediterranean plants for inhibitors of the enzyme. Strongest inhibitory activity was found in leaf extracts of
Cercis siliquastrum.</description><subject>Aldose-Ketose Isomerases - antagonists & inhibitors</subject><subject>Aldose-Ketose Isomerases - chemistry</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibiotic</subject><subject>Antimalarials</subject><subject>Antimalarials - chemistry</subject><subject>Cercis siliquastrum</subject><subject>Deoxyxylulose inhibitors of 2C-methyl-D-erythritol 4-phosphate sythase (IspCprotein)</subject><subject>Escherichia coli - enzymology</subject><subject>Escherichia coli - genetics</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Medicinal plants</subject><subject>Mediterranean Region</subject><subject>Molecular Sequence Data</subject><subject>Multienzyme Complexes - antagonists & inhibitors</subject><subject>Multienzyme Complexes - chemistry</subject><subject>Oxidoreductases - antagonists & inhibitors</subject><subject>Oxidoreductases - chemistry</subject><subject>Phytotherapy</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Leaves</subject><subject>Plants, Medicinal</subject><subject>Plasmodium falciparum - enzymology</subject><subject>Plasmodium falciparum - genetics</subject><subject>Terpene</subject><subject>Terpenes</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ktuqEzEUhoMo7lp9A5GAIHqRMZlkMo0XQikeNmzxQgXvQpqs6aTMZGYnqdBn8KVNaRGEIrkIZH3_OmT9CD1ntGKUybf7au6PI7iqplRWrK4oWz1ACybZilDV_HyIFlQJQVrG-A16ktKeUiZUSx-jG9bWilO1WqDf65A9Gc1gojcDdvGww9nEHeT0Dn-zESD4sMPdFLEPvd_6PMWEpw7XGzJC7o8DwY5APOY-ltiABZn7Kc29yYDTMeTeJMCvb9O8wXOcMvjwpmTCX8D5DDGaACbgeTAhp6foUWeGBM8u9xL9-Pjh--Yzufv66XazviNWyCYT7hrVSC4bzowUNW_AOKdqXlvedlvXtF1ru1qoFbRWbA1YpVzXUqCwAhCM8iV6dc5bGro_QMp69MnCUJqA6ZB0S-tWyVJiiV6ewZ0ZQPvQTTkae4L1mkkupGRcFYpcoXYQIJphCtD58vwPX13hy3EwentVIM4CG6eUInR6jn408agZ1Scv6L0-e0GfvKBZrYsXiuzFZczD9hT7K7osvwDvzwCUz_7lIepkPQRbVhPBZu0m__8KfwBvO8do</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Kaiser, J.</creator><creator>Yassin, M.</creator><creator>Prakash, S.</creator><creator>Safi, N.</creator><creator>Agami, M.</creator><creator>Lauw, S.</creator><creator>Ostrozhenkova, E.</creator><creator>Bacher, A.</creator><creator>Rohdich, F.</creator><creator>Eisenreich, W.</creator><creator>Safi, J.</creator><creator>Golan-Goldhirsh, A.</creator><general>Elsevier GmbH</general><general>Urban & Fischer 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>20070401</creationdate><title>Anti-malarial drug targets: Screening for inhibitors of 2C-methyl- d-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants</title><author>Kaiser, J. ; Yassin, M. ; Prakash, S. ; Safi, N. ; Agami, M. ; Lauw, S. ; Ostrozhenkova, E. ; Bacher, A. ; Rohdich, F. ; Eisenreich, W. ; Safi, J. ; Golan-Goldhirsh, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-3d595636531a64235eadd9232c37fbd57f7cf2498e7c4baec99df70e0e8ee4103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aldose-Ketose Isomerases - antagonists & inhibitors</topic><topic>Aldose-Ketose Isomerases - chemistry</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibiotic</topic><topic>Antimalarials</topic><topic>Antimalarials - chemistry</topic><topic>Cercis siliquastrum</topic><topic>Deoxyxylulose inhibitors of 2C-methyl-D-erythritol 4-phosphate sythase (IspCprotein)</topic><topic>Escherichia coli - enzymology</topic><topic>Escherichia coli - genetics</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Medicinal plants</topic><topic>Mediterranean Region</topic><topic>Molecular Sequence Data</topic><topic>Multienzyme Complexes - antagonists & inhibitors</topic><topic>Multienzyme Complexes - chemistry</topic><topic>Oxidoreductases - antagonists & inhibitors</topic><topic>Oxidoreductases - chemistry</topic><topic>Phytotherapy</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Leaves</topic><topic>Plants, Medicinal</topic><topic>Plasmodium falciparum - enzymology</topic><topic>Plasmodium falciparum - genetics</topic><topic>Terpene</topic><topic>Terpenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaiser, J.</creatorcontrib><creatorcontrib>Yassin, M.</creatorcontrib><creatorcontrib>Prakash, S.</creatorcontrib><creatorcontrib>Safi, N.</creatorcontrib><creatorcontrib>Agami, M.</creatorcontrib><creatorcontrib>Lauw, S.</creatorcontrib><creatorcontrib>Ostrozhenkova, E.</creatorcontrib><creatorcontrib>Bacher, A.</creatorcontrib><creatorcontrib>Rohdich, F.</creatorcontrib><creatorcontrib>Eisenreich, W.</creatorcontrib><creatorcontrib>Safi, J.</creatorcontrib><creatorcontrib>Golan-Goldhirsh, A.</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>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaiser, J.</au><au>Yassin, M.</au><au>Prakash, S.</au><au>Safi, N.</au><au>Agami, M.</au><au>Lauw, S.</au><au>Ostrozhenkova, E.</au><au>Bacher, A.</au><au>Rohdich, F.</au><au>Eisenreich, W.</au><au>Safi, J.</au><au>Golan-Goldhirsh, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-malarial drug targets: Screening for inhibitors of 2C-methyl- d-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>14</volume><issue>4</issue><spage>242</spage><epage>249</epage><pages>242-249</pages><issn>0944-7113</issn><eissn>1618-095X</eissn><abstract>The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in numerous pathogenic eubacteria and in apicoplast-type protozoa, most notably
Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective chemotherapy. The first committed step of the non-mevalonate pathway is catalyzed by 2C-methyl-
d-erythritol 4-phosphate synthase (IspC). Using photometric and NMR spectroscopic assays, we screened extracts of Mediterranean plants for inhibitors of the enzyme. Strongest inhibitory activity was found in leaf extracts of
Cercis siliquastrum.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>17293098</pmid><doi>10.1016/j.phymed.2006.12.018</doi><tpages>8</tpages></addata></record> |
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| ispartof | Phytomedicine (Stuttgart), 2007-04, Vol.14 (4), p.242-249 |
| issn | 0944-7113 1618-095X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70279656 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aldose-Ketose Isomerases - antagonists & inhibitors Aldose-Ketose Isomerases - chemistry Amino Acid Sequence Animals Antibiotic Antimalarials Antimalarials - chemistry Cercis siliquastrum Deoxyxylulose inhibitors of 2C-methyl-D-erythritol 4-phosphate sythase (IspCprotein) Escherichia coli - enzymology Escherichia coli - genetics Health aspects Humans Malaria Malaria, Falciparum - drug therapy Medicinal plants Mediterranean Region Molecular Sequence Data Multienzyme Complexes - antagonists & inhibitors Multienzyme Complexes - chemistry Oxidoreductases - antagonists & inhibitors Oxidoreductases - chemistry Phytotherapy Plant Extracts - chemistry Plant Leaves Plants, Medicinal Plasmodium falciparum - enzymology Plasmodium falciparum - genetics Terpene Terpenes |
| title | Anti-malarial drug targets: Screening for inhibitors of 2C-methyl- d-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants |
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