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Targeting DHFR in parasitic protozoa
Dihydrofolate reductase inhibitors are the mainstay in the fight against malaria and toxoplasmosis, but new inhibitors will be needed for resistant strains and for cryptosporidiosis, an emerging infectious disease. Parasitic apicomplexans are responsible for some of the most severe worldwide health...
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| Published in: | Drug Discovery Today 2005-01, Vol.10 (2), p.121-128 |
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| Language: | English |
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| container_end_page | 128 |
| container_issue | 2 |
| container_start_page | 121 |
| container_title | Drug Discovery Today |
| container_volume | 10 |
| creator | Anderson, Amy C. |
| description | Dihydrofolate reductase inhibitors are the mainstay in the fight against malaria and toxoplasmosis, but new inhibitors will be needed for resistant strains and for cryptosporidiosis, an emerging infectious disease.
Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development. |
| doi_str_mv | 10.1016/S1359-6446(04)03308-2 |
| format | article |
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Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.</description><identifier>ISSN: 1359-6446</identifier><identifier>EISSN: 1878-5832</identifier><identifier>DOI: 10.1016/S1359-6446(04)03308-2</identifier><identifier>PMID: 15718161</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Antiprotozoal Agents - pharmacology ; Antiprotozoal Agents - therapeutic use ; Biological and medical sciences ; Clinical Trials as Topic ; Cryptosporidiosis ; Enzyme inhibitors ; Eukaryota - drug effects ; Eukaryota - enzymology ; Eukaryota - physiology ; Folic Acid Antagonists - pharmacology ; Folic Acid Antagonists - therapeutic use ; General pharmacology ; Humans ; Malaria ; Medical sciences ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Protozoan Infections - drug therapy ; Protozoan Infections - enzymology ; Structure-based drug design ; Tetrahydrofolate Dehydrogenase - chemistry ; Tetrahydrofolate Dehydrogenase - metabolism ; Toxoplasmosis</subject><ispartof>Drug Discovery Today, 2005-01, Vol.10 (2), p.121-128</ispartof><rights>2005 Elsevier Ltd</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-4ea419be71f0fcec20e840a931c7d98c9aab20f35a83159c4b30f366751c09fc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>313,314,780,784,792,27922,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16390310$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15718161$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anderson, Amy C.</creatorcontrib><title>Targeting DHFR in parasitic protozoa</title><title>Drug Discovery Today</title><addtitle>Drug Discov Today</addtitle><description>Dihydrofolate reductase inhibitors are the mainstay in the fight against malaria and toxoplasmosis, but new inhibitors will be needed for resistant strains and for cryptosporidiosis, an emerging infectious disease.
Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.</description><subject>Animals</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Antiprotozoal Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Clinical Trials as Topic</subject><subject>Cryptosporidiosis</subject><subject>Enzyme inhibitors</subject><subject>Eukaryota - drug effects</subject><subject>Eukaryota - enzymology</subject><subject>Eukaryota - physiology</subject><subject>Folic Acid Antagonists - pharmacology</subject><subject>Folic Acid Antagonists - therapeutic use</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Malaria</subject><subject>Medical sciences</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Protozoan Infections - drug therapy</subject><subject>Protozoan Infections - enzymology</subject><subject>Structure-based drug design</subject><subject>Tetrahydrofolate Dehydrogenase - chemistry</subject><subject>Tetrahydrofolate Dehydrogenase - metabolism</subject><subject>Toxoplasmosis</subject><issn>1359-6446</issn><issn>1878-5832</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkE1LAzEQhoMotlZ_gtKDih5WZzYfm5xE6keFgqD1HLJptkTa3ZpsBf31btuVHnuaGXjemeEh5BThBgHF7TtSrhLBmLgCdg2UgkzSPdJFmcmES5ruN_0_0iFHMX4CYKq4OCQd5BlKFNgl52MTpq725bT_MHx66_uyvzDBRF9721-Eqq5-K3NMDgozi-6krT3y8fQ4HgyT0evzy-B-lFiWsjphzjBUucuwgMI6m4KTDIyiaLOJklYZk6dQUG4kRa4sy2kzCZFxtKAKS3vkcrO3Ofy1dLHWcx-tm81M6apl1CJjjIPAnSBmkkuhViDfgDZUMQZX6EXwcxN-NIJeedRrj3olSQPTa486bXJn7YFlPneTbaoV1wAXLWCiNbMimNL6uOUEVUARGu5uw7nG27d3QUfrXWndxAdnaz2p_I5X_gA9pYzT</recordid><startdate>20050115</startdate><enddate>20050115</enddate><creator>Anderson, Amy C.</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050115</creationdate><title>Targeting DHFR in parasitic protozoa</title><author>Anderson, Amy C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-4ea419be71f0fcec20e840a931c7d98c9aab20f35a83159c4b30f366751c09fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antiprotozoal Agents - pharmacology</topic><topic>Antiprotozoal Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Clinical Trials as Topic</topic><topic>Cryptosporidiosis</topic><topic>Enzyme inhibitors</topic><topic>Eukaryota - drug effects</topic><topic>Eukaryota - enzymology</topic><topic>Eukaryota - physiology</topic><topic>Folic Acid Antagonists - pharmacology</topic><topic>Folic Acid Antagonists - therapeutic use</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Malaria</topic><topic>Medical sciences</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Protozoan Infections - drug therapy</topic><topic>Protozoan Infections - enzymology</topic><topic>Structure-based drug design</topic><topic>Tetrahydrofolate Dehydrogenase - chemistry</topic><topic>Tetrahydrofolate Dehydrogenase - metabolism</topic><topic>Toxoplasmosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anderson, Amy C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Drug Discovery Today</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anderson, Amy C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting DHFR in parasitic protozoa</atitle><jtitle>Drug Discovery Today</jtitle><addtitle>Drug Discov Today</addtitle><date>2005-01-15</date><risdate>2005</risdate><volume>10</volume><issue>2</issue><spage>121</spage><epage>128</epage><pages>121-128</pages><issn>1359-6446</issn><eissn>1878-5832</eissn><abstract>Dihydrofolate reductase inhibitors are the mainstay in the fight against malaria and toxoplasmosis, but new inhibitors will be needed for resistant strains and for cryptosporidiosis, an emerging infectious disease.
Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15718161</pmid><doi>10.1016/S1359-6446(04)03308-2</doi><tpages>8</tpages></addata></record> |
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| ispartof | Drug Discovery Today, 2005-01, Vol.10 (2), p.121-128 |
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| language | eng |
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| source | ScienceDirect Freedom Collection |
| subjects | Animals Antiprotozoal Agents - pharmacology Antiprotozoal Agents - therapeutic use Biological and medical sciences Clinical Trials as Topic Cryptosporidiosis Enzyme inhibitors Eukaryota - drug effects Eukaryota - enzymology Eukaryota - physiology Folic Acid Antagonists - pharmacology Folic Acid Antagonists - therapeutic use General pharmacology Humans Malaria Medical sciences Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Protozoan Infections - drug therapy Protozoan Infections - enzymology Structure-based drug design Tetrahydrofolate Dehydrogenase - chemistry Tetrahydrofolate Dehydrogenase - metabolism Toxoplasmosis |
| title | Targeting DHFR in parasitic protozoa |
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