Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells
A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower s...
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| Veröffentlicht in: | Journal of medicinal chemistry 2009-02, Vol.52 (4), p.1198-1203 |
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| container_title | Journal of medicinal chemistry |
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| creator | Rosenthal, Andrew S Chen, Xiaochun Liu, Jun O West, Diana C Hergenrother, Paul J Shapiro, Theresa A Posner, Gary H |
| description | A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines. |
| doi_str_mv | 10.1021/jm801484v |
| format | Article |
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One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm801484v</identifier><identifier>PMID: 19186946</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Columbus, OH: American Chemical Society</publisher><subject>Administration, Oral ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials - administration & dosage ; Antimalarials - pharmacology ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Antiparasitic agents ; Artemisinins ; Biological and medical sciences ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Drug Stability ; Drug Therapy, Combination ; General aspects ; Humans ; Malaria - drug therapy ; Medical sciences ; Mefloquine - administration & dosage ; Mefloquine - pharmacology ; Mice ; Pharmacology. Drug treatments ; Sulfones - administration & dosage ; Sulfones - pharmacology</subject><ispartof>Journal of medicinal chemistry, 2009-02, Vol.52 (4), p.1198-1203</ispartof><rights>Copyright © 2009 American Chemical Society</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a499t-2826cb20ef67ebf8e1dd3f121c156add65ce2831f1f2933940e9838e1cdfe93a3</citedby><cites>FETCH-LOGICAL-a499t-2826cb20ef67ebf8e1dd3f121c156add65ce2831f1f2933940e9838e1cdfe93a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm801484v$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm801484v$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21190518$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19186946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rosenthal, Andrew S</creatorcontrib><creatorcontrib>Chen, Xiaochun</creatorcontrib><creatorcontrib>Liu, Jun O</creatorcontrib><creatorcontrib>West, Diana C</creatorcontrib><creatorcontrib>Hergenrother, Paul J</creatorcontrib><creatorcontrib>Shapiro, Theresa A</creatorcontrib><creatorcontrib>Posner, Gary H</creatorcontrib><title>Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - pharmacology</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiparasitic agents</subject><subject>Artemisinins</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Drug Stability</subject><subject>Drug Therapy, Combination</subject><subject>General aspects</subject><subject>Humans</subject><subject>Malaria - drug therapy</subject><subject>Medical sciences</subject><subject>Mefloquine - administration & dosage</subject><subject>Mefloquine - pharmacology</subject><subject>Mice</subject><subject>Pharmacology. Drug treatments</subject><subject>Sulfones - administration & dosage</subject><subject>Sulfones - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkctuEzEUhi0EoiGw4AWQNyCxGPBl4tgbpGhKoVJLkVLE0nI8x40jz7i1Z9LmVfq0GBqlILGyjvzpO5cfodeUfKCE0Y-bThJay3r7BE3ojJGqlqR-iiaEMFYxwfgRepHzhhDCKePP0RFVVApViwm6PzfBJG-q096BHaDF594CXiTAzZhKudphg5e-vwqAL5IJ-DhmwNHhb3CLj30HyVt8mXy8Mz3g5Rhc7CHjn2tv1380i5AjXkIodr-FUHR9i7_HW0huDKVsdkMc4l2xDBE3preQcAMh5JfomTMhw6v9O0U_Tj5fNl-rs4svp83irDK1UkPFJBN2xQg4MYeVk0DbljvKqKUzYdpWzCwwyamjjinOVU1ASV4w2zpQ3PAp-vTgvR5XHbQW-qHsqa-T70za6Wi8_ven92t9FbeaCSVJcU7Ru70gxZsR8qA7n21ZoVwkjlmLOZeiVvMCvn8AbYo5J3CHJpTo30nqQ5KFffP3VI_kProCvN0DJlsTXCqn8_nAMUoVmVH5yBmb9SaOqS_H_E_DX63CtHo</recordid><startdate>20090226</startdate><enddate>20090226</enddate><creator>Rosenthal, Andrew S</creator><creator>Chen, Xiaochun</creator><creator>Liu, Jun O</creator><creator>West, Diana C</creator><creator>Hergenrother, Paul J</creator><creator>Shapiro, Theresa A</creator><creator>Posner, Gary H</creator><general>American Chemical Society</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>5PM</scope></search><sort><creationdate>20090226</creationdate><title>Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells</title><author>Rosenthal, Andrew S ; Chen, Xiaochun ; Liu, Jun O ; West, Diana C ; Hergenrother, Paul J ; Shapiro, Theresa A ; Posner, Gary H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a499t-2826cb20ef67ebf8e1dd3f121c156add65ce2831f1f2933940e9838e1cdfe93a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antimalarials - administration & dosage</topic><topic>Antimalarials - pharmacology</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiparasitic agents</topic><topic>Artemisinins</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Drug Stability</topic><topic>Drug Therapy, Combination</topic><topic>General aspects</topic><topic>Humans</topic><topic>Malaria - drug therapy</topic><topic>Medical sciences</topic><topic>Mefloquine - administration & dosage</topic><topic>Mefloquine - pharmacology</topic><topic>Mice</topic><topic>Pharmacology. Drug treatments</topic><topic>Sulfones - administration & dosage</topic><topic>Sulfones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rosenthal, Andrew S</creatorcontrib><creatorcontrib>Chen, Xiaochun</creatorcontrib><creatorcontrib>Liu, Jun O</creatorcontrib><creatorcontrib>West, Diana C</creatorcontrib><creatorcontrib>Hergenrother, Paul J</creatorcontrib><creatorcontrib>Shapiro, Theresa A</creatorcontrib><creatorcontrib>Posner, Gary H</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>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rosenthal, Andrew S</au><au>Chen, Xiaochun</au><au>Liu, Jun O</au><au>West, Diana C</au><au>Hergenrother, Paul J</au><au>Shapiro, Theresa A</au><au>Posner, Gary H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2009-02-26</date><risdate>2009</risdate><volume>52</volume><issue>4</issue><spage>1198</spage><epage>1203</epage><pages>1198-1203</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19186946</pmid><doi>10.1021/jm801484v</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of medicinal chemistry, 2009-02, Vol.52 (4), p.1198-1203 |
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| source | MEDLINE; ACS Publications |
| subjects | Administration, Oral Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antimalarials - administration & dosage Antimalarials - pharmacology Antineoplastic agents Antineoplastic Agents - pharmacology Antiparasitic agents Artemisinins Biological and medical sciences Cell Line, Tumor Drug Screening Assays, Antitumor Drug Stability Drug Therapy, Combination General aspects Humans Malaria - drug therapy Medical sciences Mefloquine - administration & dosage Mefloquine - pharmacology Mice Pharmacology. Drug treatments Sulfones - administration & dosage Sulfones - pharmacology |
| title | Malaria-Infected Mice Are Cured by a Single Oral Dose of New Dimeric Trioxane Sulfones Which Are Also Selectively and Powerfully Cytotoxic to Cancer Cells |
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