Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH
Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-03, Vol.22 (5), p.1985-1988 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1988 |
|---|---|
| container_issue | 5 |
| container_start_page | 1985 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 22 |
| creator | Kirubakaran, Sivapriya Gorla, Suresh Kumar Sharling, Lisa Zhang, Minjia Liu, Xiaoping Ray, Soumya S. MacPherson, Iain S. Striepen, Boris Hedstrom, Lizbeth Cuny, Gregory D. |
| description | Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure–activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro. |
| doi_str_mv | 10.1016/j.bmcl.2012.01.029 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3289519</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X12000625</els_id><sourcerecordid>926885756</sourcerecordid><originalsourceid>FETCH-LOGICAL-c582t-7af54b2ec9c380fd9856f87a2c0820531f1308416520241c1b2089693a0c9e663</originalsourceid><addsrcrecordid>eNqNkc-q1DAUh4so3vHqC7iQbsRV60maZBIQQcY_98IVBRXchTQ9dTK0TU3Sgbkr38E39ElsmfGqG3F1Fuc7v3OSL8seEigJEPF0V9a97UoKhJZASqDqVrYiTLCiYsBvZytQAgqp2Oez7F6MOwDCgLG72RmlFQFK1SqLH1KYbJoC_vj23djk9i4d8oCdSc4PcevGPKapOeS-zSN2uBCY1zhcu9415tp3WNQmYpO7Yetql3yIC7sJhzH5OPrgGjf1-WjCfi6Xb9-_vLif3WlNF_HBqZ5nn16_-ri5KK7evbncvLgqLJc0FWvTclZTtMpWEtpGSS5auTbUgqTAK9KSCiQjglOgjFhSU5BKqMqAVShEdZ49P-aOU91jY3FIwXR6DK434aC9cfrvzuC2-ovf64pKxYmaA56cAoL_OmFMunfRYteZAf0UtaJCSr7m4j9IuhZ0TRaSHkkbfIwB25t7COhFq97pRatetGogetY6Dz368yU3I788zsDjE2CiNV0bzGBd_M3xeTnn1cw9O3I4__veYdDROhwsNi7MbnXj3b_u-AlWUsRE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>922762716</pqid></control><display><type>article</type><title>Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Kirubakaran, Sivapriya ; Gorla, Suresh Kumar ; Sharling, Lisa ; Zhang, Minjia ; Liu, Xiaoping ; Ray, Soumya S. ; MacPherson, Iain S. ; Striepen, Boris ; Hedstrom, Lizbeth ; Cuny, Gregory D.</creator><creatorcontrib>Kirubakaran, Sivapriya ; Gorla, Suresh Kumar ; Sharling, Lisa ; Zhang, Minjia ; Liu, Xiaoping ; Ray, Soumya S. ; MacPherson, Iain S. ; Striepen, Boris ; Hedstrom, Lizbeth ; Cuny, Gregory D.</creatorcontrib><description>Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure–activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2012.01.029</identifier><identifier>PMID: 22310229</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiparasitic agents ; Antiparasitic Agents - chemical synthesis ; Antiparasitic Agents - chemistry ; Antiparasitic Agents - pharmacology ; Benzimidazole ; Benzimidazoles - chemical synthesis ; Benzimidazoles - chemistry ; Benzimidazoles - pharmacology ; Biological and medical sciences ; Cryptosporidiosis - drug therapy ; Cryptosporidium ; Cryptosporidium parvum ; Cryptosporidium parvum - drug effects ; Cryptosporidium parvum - enzymology ; dehydrogenase ; Genomes ; Guanine ; Humans ; IMP Dehydrogenase - antagonists & inhibitors ; IMP Dehydrogenase - metabolism ; Infection ; Inhibitor ; Inosine 5′-monophosphate dehydrogenase (IMPDH) ; Medical sciences ; Nucleotides ; Parasite ; Parasites ; Pathogens ; Pharmacology. Drug treatments ; Protozoan ; Structure-Activity Relationship ; Structure-activity relationships</subject><ispartof>Bioorganic & medicinal chemistry letters, 2012-03, Vol.22 (5), p.1985-1988</ispartof><rights>2012 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><rights>2012 Elsevier Ltd. All rights reserved 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-7af54b2ec9c380fd9856f87a2c0820531f1308416520241c1b2089693a0c9e663</citedby><cites>FETCH-LOGICAL-c582t-7af54b2ec9c380fd9856f87a2c0820531f1308416520241c1b2089693a0c9e663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X12000625$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25627553$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22310229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kirubakaran, Sivapriya</creatorcontrib><creatorcontrib>Gorla, Suresh Kumar</creatorcontrib><creatorcontrib>Sharling, Lisa</creatorcontrib><creatorcontrib>Zhang, Minjia</creatorcontrib><creatorcontrib>Liu, Xiaoping</creatorcontrib><creatorcontrib>Ray, Soumya S.</creatorcontrib><creatorcontrib>MacPherson, Iain S.</creatorcontrib><creatorcontrib>Striepen, Boris</creatorcontrib><creatorcontrib>Hedstrom, Lizbeth</creatorcontrib><creatorcontrib>Cuny, Gregory D.</creatorcontrib><title>Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure–activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiparasitic agents</subject><subject>Antiparasitic Agents - chemical synthesis</subject><subject>Antiparasitic Agents - chemistry</subject><subject>Antiparasitic Agents - pharmacology</subject><subject>Benzimidazole</subject><subject>Benzimidazoles - chemical synthesis</subject><subject>Benzimidazoles - chemistry</subject><subject>Benzimidazoles - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cryptosporidiosis - drug therapy</subject><subject>Cryptosporidium</subject><subject>Cryptosporidium parvum</subject><subject>Cryptosporidium parvum - drug effects</subject><subject>Cryptosporidium parvum - enzymology</subject><subject>dehydrogenase</subject><subject>Genomes</subject><subject>Guanine</subject><subject>Humans</subject><subject>IMP Dehydrogenase - antagonists & inhibitors</subject><subject>IMP Dehydrogenase - metabolism</subject><subject>Infection</subject><subject>Inhibitor</subject><subject>Inosine 5′-monophosphate dehydrogenase (IMPDH)</subject><subject>Medical sciences</subject><subject>Nucleotides</subject><subject>Parasite</subject><subject>Parasites</subject><subject>Pathogens</subject><subject>Pharmacology. Drug treatments</subject><subject>Protozoan</subject><subject>Structure-Activity Relationship</subject><subject>Structure-activity relationships</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc-q1DAUh4so3vHqC7iQbsRV60maZBIQQcY_98IVBRXchTQ9dTK0TU3Sgbkr38E39ElsmfGqG3F1Fuc7v3OSL8seEigJEPF0V9a97UoKhJZASqDqVrYiTLCiYsBvZytQAgqp2Oez7F6MOwDCgLG72RmlFQFK1SqLH1KYbJoC_vj23djk9i4d8oCdSc4PcevGPKapOeS-zSN2uBCY1zhcu9415tp3WNQmYpO7Yetql3yIC7sJhzH5OPrgGjf1-WjCfi6Xb9-_vLif3WlNF_HBqZ5nn16_-ri5KK7evbncvLgqLJc0FWvTclZTtMpWEtpGSS5auTbUgqTAK9KSCiQjglOgjFhSU5BKqMqAVShEdZ49P-aOU91jY3FIwXR6DK434aC9cfrvzuC2-ovf64pKxYmaA56cAoL_OmFMunfRYteZAf0UtaJCSr7m4j9IuhZ0TRaSHkkbfIwB25t7COhFq97pRatetGogetY6Dz368yU3I788zsDjE2CiNV0bzGBd_M3xeTnn1cw9O3I4__veYdDROhwsNi7MbnXj3b_u-AlWUsRE</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Kirubakaran, Sivapriya</creator><creator>Gorla, Suresh Kumar</creator><creator>Sharling, Lisa</creator><creator>Zhang, Minjia</creator><creator>Liu, Xiaoping</creator><creator>Ray, Soumya S.</creator><creator>MacPherson, Iain S.</creator><creator>Striepen, Boris</creator><creator>Hedstrom, Lizbeth</creator><creator>Cuny, Gregory D.</creator><general>Elsevier Ltd</general><general>Elsevier</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20120301</creationdate><title>Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH</title><author>Kirubakaran, Sivapriya ; Gorla, Suresh Kumar ; Sharling, Lisa ; Zhang, Minjia ; Liu, Xiaoping ; Ray, Soumya S. ; MacPherson, Iain S. ; Striepen, Boris ; Hedstrom, Lizbeth ; Cuny, Gregory D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c582t-7af54b2ec9c380fd9856f87a2c0820531f1308416520241c1b2089693a0c9e663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiparasitic agents</topic><topic>Antiparasitic Agents - chemical synthesis</topic><topic>Antiparasitic Agents - chemistry</topic><topic>Antiparasitic Agents - pharmacology</topic><topic>Benzimidazole</topic><topic>Benzimidazoles - chemical synthesis</topic><topic>Benzimidazoles - chemistry</topic><topic>Benzimidazoles - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cryptosporidiosis - drug therapy</topic><topic>Cryptosporidium</topic><topic>Cryptosporidium parvum</topic><topic>Cryptosporidium parvum - drug effects</topic><topic>Cryptosporidium parvum - enzymology</topic><topic>dehydrogenase</topic><topic>Genomes</topic><topic>Guanine</topic><topic>Humans</topic><topic>IMP Dehydrogenase - antagonists & inhibitors</topic><topic>IMP Dehydrogenase - metabolism</topic><topic>Infection</topic><topic>Inhibitor</topic><topic>Inosine 5′-monophosphate dehydrogenase (IMPDH)</topic><topic>Medical sciences</topic><topic>Nucleotides</topic><topic>Parasite</topic><topic>Parasites</topic><topic>Pathogens</topic><topic>Pharmacology. Drug treatments</topic><topic>Protozoan</topic><topic>Structure-Activity Relationship</topic><topic>Structure-activity relationships</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kirubakaran, Sivapriya</creatorcontrib><creatorcontrib>Gorla, Suresh Kumar</creatorcontrib><creatorcontrib>Sharling, Lisa</creatorcontrib><creatorcontrib>Zhang, Minjia</creatorcontrib><creatorcontrib>Liu, Xiaoping</creatorcontrib><creatorcontrib>Ray, Soumya S.</creatorcontrib><creatorcontrib>MacPherson, Iain S.</creatorcontrib><creatorcontrib>Striepen, Boris</creatorcontrib><creatorcontrib>Hedstrom, Lizbeth</creatorcontrib><creatorcontrib>Cuny, Gregory D.</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kirubakaran, Sivapriya</au><au>Gorla, Suresh Kumar</au><au>Sharling, Lisa</au><au>Zhang, Minjia</au><au>Liu, Xiaoping</au><au>Ray, Soumya S.</au><au>MacPherson, Iain S.</au><au>Striepen, Boris</au><au>Hedstrom, Lizbeth</au><au>Cuny, Gregory D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>22</volume><issue>5</issue><spage>1985</spage><epage>1988</epage><pages>1985-1988</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure–activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>22310229</pmid><doi>10.1016/j.bmcl.2012.01.029</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2012-03, Vol.22 (5), p.1985-1988 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3289519 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Antiparasitic Agents - chemical synthesis Antiparasitic Agents - chemistry Antiparasitic Agents - pharmacology Benzimidazole Benzimidazoles - chemical synthesis Benzimidazoles - chemistry Benzimidazoles - pharmacology Biological and medical sciences Cryptosporidiosis - drug therapy Cryptosporidium Cryptosporidium parvum Cryptosporidium parvum - drug effects Cryptosporidium parvum - enzymology dehydrogenase Genomes Guanine Humans IMP Dehydrogenase - antagonists & inhibitors IMP Dehydrogenase - metabolism Infection Inhibitor Inosine 5′-monophosphate dehydrogenase (IMPDH) Medical sciences Nucleotides Parasite Parasites Pathogens Pharmacology. Drug treatments Protozoan Structure-Activity Relationship Structure-activity relationships |
| title | Structure–activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T03%3A37%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structure%E2%80%93activity%20relationship%20study%20of%20selective%20benzimidazole-based%20inhibitors%20of%20Cryptosporidium%20parvum%20IMPDH&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Kirubakaran,%20Sivapriya&rft.date=2012-03-01&rft.volume=22&rft.issue=5&rft.spage=1985&rft.epage=1988&rft.pages=1985-1988&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2012.01.029&rft_dat=%3Cproquest_pubme%3E926885756%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=922762716&rft_id=info:pmid/22310229&rft_els_id=S0960894X12000625&rfr_iscdi=true |