Antimalarial activity of a 4', 5'-unsaturated 5'- fluoroadenosine mechanism-based inhibitor of s-adenosyl- l-homocysteine hydrolase
A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl- l-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated wi...
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| Veröffentlicht in: | Biochemical pharmacology 1990-08, Vol.40 (3), p.601-606 |
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| creator | Bitonti, Alan J. Baumann, Russell J. Jarvi, Esa T. McCarthy, James R. Mccann, Peter P. |
| description | A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of
S-adenosyl-
l-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of
Plasmodium falciparum in vitro and
Plasmodium berghei in mice. Inhibition of
P.
berghei growth was associated with a large increase in the concentration of
S-adenosyl-
l-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either
P.
berghei or
P.
falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria. |
| doi_str_mv | 10.1016/0006-2952(90)90562-Y |
| format | Article |
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S-adenosyl-
l-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of
Plasmodium falciparum in vitro and
Plasmodium berghei in mice. Inhibition of
P.
berghei growth was associated with a large increase in the concentration of
S-adenosyl-
l-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either
P.
berghei or
P.
falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/0006-2952(90)90562-Y</identifier><identifier>PMID: 2200410</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - pharmacology ; Adenosine - therapeutic use ; Adenosylhomocysteinase ; Animals ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; antiviral agents ; Erythrocytes - metabolism ; Hydrolases - antagonists & inhibitors ; Hydrolases - blood ; Malaria - blood ; Malaria - drug therapy ; Molecular Structure ; Plasmodium berghei ; Plasmodium berghei - drug effects ; Plasmodium berghei - growth & development ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - growth & development ; S-adenosyl-L-homocysteine hydrolase ; S-Adenosylhomocysteine - blood</subject><ispartof>Biochemical pharmacology, 1990-08, Vol.40 (3), p.601-606</ispartof><rights>1990</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-ae1d7d9b4ba0eae60839a6a9b86ba29b39c7c8f90ece2a43d234081b6278ae813</citedby><cites>FETCH-LOGICAL-c439t-ae1d7d9b4ba0eae60839a6a9b86ba29b39c7c8f90ece2a43d234081b6278ae813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0006-2952(90)90562-Y$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2200410$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bitonti, Alan J.</creatorcontrib><creatorcontrib>Baumann, Russell J.</creatorcontrib><creatorcontrib>Jarvi, Esa T.</creatorcontrib><creatorcontrib>McCarthy, James R.</creatorcontrib><creatorcontrib>Mccann, Peter P.</creatorcontrib><title>Antimalarial activity of a 4', 5'-unsaturated 5'- fluoroadenosine mechanism-based inhibitor of s-adenosyl- l-homocysteine hydrolase</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of
S-adenosyl-
l-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of
Plasmodium falciparum in vitro and
Plasmodium berghei in mice. Inhibition of
P.
berghei growth was associated with a large increase in the concentration of
S-adenosyl-
l-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either
P.
berghei or
P.
falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - pharmacology</subject><subject>Adenosine - therapeutic use</subject><subject>Adenosylhomocysteinase</subject><subject>Animals</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>antiviral agents</subject><subject>Erythrocytes - metabolism</subject><subject>Hydrolases - antagonists & inhibitors</subject><subject>Hydrolases - blood</subject><subject>Malaria - blood</subject><subject>Malaria - drug therapy</subject><subject>Molecular Structure</subject><subject>Plasmodium berghei</subject><subject>Plasmodium berghei - drug effects</subject><subject>Plasmodium berghei - growth & development</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - growth & development</subject><subject>S-adenosyl-L-homocysteine hydrolase</subject><subject>S-Adenosylhomocysteine - blood</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1rFTEUxYMo9Vn9DxRmZRWM5mNeJtkUSvELCm500VW4ydzhRTKTmmQKs_Yfd8b36FJX4eb-zrlwDiEvOXvPGVcfGGOKCrMXbwx7a9heCXr7iOy47uT6rfRjsntAnpJnpfzcRq34GTkTgrGWsx35fTXVMEKEHCA24Gu4D3Vp0tBA0168a_YXdJ4K1DlDxX4bmyHOKSfocUolTNiM6A8whTJSB2VlwnQILtSUN5dCj-ASaRPpIY3JL6XipjssfU5xlTwnTwaIBV-c3nPy49PH79df6M23z1-vr26ob6WpFJD3XW9c64AhoGJaGlBgnFYOhHHS-M7rwTD0KKCVvZAt09wp0WlAzeU5eX30vcvp14yl2jEUjzHChGkutjNGGMnlf0G-10ybtl3B9gj6nErJONi7vKaZF8uZ3UqyW-R2a8AaZv-WZG9X2auT_-xG7B9Ep1bW_eVxj2sa9wGzLT7g5LEPGX21fQr_PvAHmk-iQQ</recordid><startdate>19900801</startdate><enddate>19900801</enddate><creator>Bitonti, Alan J.</creator><creator>Baumann, Russell J.</creator><creator>Jarvi, Esa T.</creator><creator>McCarthy, James R.</creator><creator>Mccann, Peter P.</creator><general>Elsevier Inc</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>7QL</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19900801</creationdate><title>Antimalarial activity of a 4', 5'-unsaturated 5'- fluoroadenosine mechanism-based inhibitor of s-adenosyl- l-homocysteine hydrolase</title><author>Bitonti, Alan J. ; Baumann, Russell J. ; Jarvi, Esa T. ; McCarthy, James R. ; Mccann, Peter P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-ae1d7d9b4ba0eae60839a6a9b86ba29b39c7c8f90ece2a43d234081b6278ae813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - pharmacology</topic><topic>Adenosine - therapeutic use</topic><topic>Adenosylhomocysteinase</topic><topic>Animals</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>antiviral agents</topic><topic>Erythrocytes - metabolism</topic><topic>Hydrolases - antagonists & inhibitors</topic><topic>Hydrolases - blood</topic><topic>Malaria - blood</topic><topic>Malaria - drug therapy</topic><topic>Molecular Structure</topic><topic>Plasmodium berghei</topic><topic>Plasmodium berghei - drug effects</topic><topic>Plasmodium berghei - growth & development</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - growth & development</topic><topic>S-adenosyl-L-homocysteine hydrolase</topic><topic>S-Adenosylhomocysteine - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bitonti, Alan J.</creatorcontrib><creatorcontrib>Baumann, Russell J.</creatorcontrib><creatorcontrib>Jarvi, Esa T.</creatorcontrib><creatorcontrib>McCarthy, James R.</creatorcontrib><creatorcontrib>Mccann, Peter P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bitonti, Alan J.</au><au>Baumann, Russell J.</au><au>Jarvi, Esa T.</au><au>McCarthy, James R.</au><au>Mccann, Peter P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimalarial activity of a 4', 5'-unsaturated 5'- fluoroadenosine mechanism-based inhibitor of s-adenosyl- l-homocysteine hydrolase</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1990-08-01</date><risdate>1990</risdate><volume>40</volume><issue>3</issue><spage>601</spage><epage>606</epage><pages>601-606</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><abstract>A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of
S-adenosyl-
l-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of
Plasmodium falciparum in vitro and
Plasmodium berghei in mice. Inhibition of
P.
berghei growth was associated with a large increase in the concentration of
S-adenosyl-
l-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either
P.
berghei or
P.
falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>2200410</pmid><doi>10.1016/0006-2952(90)90562-Y</doi><tpages>6</tpages></addata></record> |
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| ispartof | Biochemical pharmacology, 1990-08, Vol.40 (3), p.601-606 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Adenosine - analogs & derivatives Adenosine - pharmacology Adenosine - therapeutic use Adenosylhomocysteinase Animals Antimalarials - pharmacology Antimalarials - therapeutic use antiviral agents Erythrocytes - metabolism Hydrolases - antagonists & inhibitors Hydrolases - blood Malaria - blood Malaria - drug therapy Molecular Structure Plasmodium berghei Plasmodium berghei - drug effects Plasmodium berghei - growth & development Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - growth & development S-adenosyl-L-homocysteine hydrolase S-Adenosylhomocysteine - blood |
| title | Antimalarial activity of a 4', 5'-unsaturated 5'- fluoroadenosine mechanism-based inhibitor of s-adenosyl- l-homocysteine hydrolase |
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