View in EDS PDF Full Text

Identification of an antimalarial synthetic trioxolane drug development candidate.

Saved in:
Bibliographic Details
Title: Identification of an antimalarial synthetic trioxolane drug development candidate.
Authors: Vennerstrom, Jonathan L., Arbe-Barnes, Sarah, Brun, Reto, Charman, Susan A., Chiu, Francis C. K., Chollet, Jacques, Dong, Yuxiang, Dorn, Arnulf, Hunziker, Daniel, Matile, Hugues, McIntosh, Kylie, Padmanilayam, Maniyan, Tomas, Josefina Santo, Scheurer, Christian, Scorneaux, Bernard, Tang, Yuanqing, Urwyler, Heinrich, Wittlin, Sergio, Charman, William N.
Source: Nature. 8/19/2004, Vol. 430 Issue 7002, p900-904. 5p.
Subjects: Antimalarials, Antiparasitic agents, Drug therapy, Pharmacokinetics, Pharmacology, Stomach, Reticulum (Ruminants)
Abstract: The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which-the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)-may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Links:
  – Type: pdflink
Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 14162047
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Identification of an antimalarial synthetic trioxolane drug development candidate.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Vennerstrom%2C+Jonathan+L%2E%22">Vennerstrom, Jonathan L.</searchLink><br /><searchLink fieldCode="AR" term="%22Arbe-Barnes%2C+Sarah%22">Arbe-Barnes, Sarah</searchLink><br /><searchLink fieldCode="AR" term="%22Brun%2C+Reto%22">Brun, Reto</searchLink><br /><searchLink fieldCode="AR" term="%22Charman%2C+Susan+A%2E%22">Charman, Susan A.</searchLink><br /><searchLink fieldCode="AR" term="%22Chiu%2C+Francis+C%2E+K%2E%22">Chiu, Francis C. K.</searchLink><br /><searchLink fieldCode="AR" term="%22Chollet%2C+Jacques%22">Chollet, Jacques</searchLink><br /><searchLink fieldCode="AR" term="%22Dong%2C+Yuxiang%22">Dong, Yuxiang</searchLink><br /><searchLink fieldCode="AR" term="%22Dorn%2C+Arnulf%22">Dorn, Arnulf</searchLink><br /><searchLink fieldCode="AR" term="%22Hunziker%2C+Daniel%22">Hunziker, Daniel</searchLink><br /><searchLink fieldCode="AR" term="%22Matile%2C+Hugues%22">Matile, Hugues</searchLink><br /><searchLink fieldCode="AR" term="%22McIntosh%2C+Kylie%22">McIntosh, Kylie</searchLink><br /><searchLink fieldCode="AR" term="%22Padmanilayam%2C+Maniyan%22">Padmanilayam, Maniyan</searchLink><br /><searchLink fieldCode="AR" term="%22Tomas%2C+Josefina+Santo%22">Tomas, Josefina Santo</searchLink><br /><searchLink fieldCode="AR" term="%22Scheurer%2C+Christian%22">Scheurer, Christian</searchLink><br /><searchLink fieldCode="AR" term="%22Scorneaux%2C+Bernard%22">Scorneaux, Bernard</searchLink><br /><searchLink fieldCode="AR" term="%22Tang%2C+Yuanqing%22">Tang, Yuanqing</searchLink><br /><searchLink fieldCode="AR" term="%22Urwyler%2C+Heinrich%22">Urwyler, Heinrich</searchLink><br /><searchLink fieldCode="AR" term="%22Wittlin%2C+Sergio%22">Wittlin, Sergio</searchLink><br /><searchLink fieldCode="AR" term="%22Charman%2C+William+N%2E%22">Charman, William N.</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 8/19/2004, Vol. 430 Issue 7002, p900-904. 5p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Antimalarials%22">Antimalarials</searchLink><br /><searchLink fieldCode="DE" term="%22Antiparasitic+agents%22">Antiparasitic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+therapy%22">Drug therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacokinetics%22">Pharmacokinetics</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacology%22">Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22Stomach%22">Stomach</searchLink><br /><searchLink fieldCode="DE" term="%22Reticulum+%28Ruminants%29%22">Reticulum (Ruminants)</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which-the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)-may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=14162047
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1038/nature02779
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 5
        StartPage: 900
    Subjects:
      – SubjectFull: Antimalarials
        Type: general
      – SubjectFull: Antiparasitic agents
        Type: general
      – SubjectFull: Drug therapy
        Type: general
      – SubjectFull: Pharmacokinetics
        Type: general
      – SubjectFull: Pharmacology
        Type: general
      – SubjectFull: Stomach
        Type: general
      – SubjectFull: Reticulum (Ruminants)
        Type: general
    Titles:
      – TitleFull: Identification of an antimalarial synthetic trioxolane drug development candidate.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Vennerstrom, Jonathan L.
      – PersonEntity:
          Name:
            NameFull: Arbe-Barnes, Sarah
      – PersonEntity:
          Name:
            NameFull: Brun, Reto
      – PersonEntity:
          Name:
            NameFull: Charman, Susan A.
      – PersonEntity:
          Name:
            NameFull: Chiu, Francis C. K.
      – PersonEntity:
          Name:
            NameFull: Chollet, Jacques
      – PersonEntity:
          Name:
            NameFull: Dong, Yuxiang
      – PersonEntity:
          Name:
            NameFull: Dorn, Arnulf
      – PersonEntity:
          Name:
            NameFull: Hunziker, Daniel
      – PersonEntity:
          Name:
            NameFull: Matile, Hugues
      – PersonEntity:
          Name:
            NameFull: McIntosh, Kylie
      – PersonEntity:
          Name:
            NameFull: Padmanilayam, Maniyan
      – PersonEntity:
          Name:
            NameFull: Tomas, Josefina Santo
      – PersonEntity:
          Name:
            NameFull: Scheurer, Christian
      – PersonEntity:
          Name:
            NameFull: Scorneaux, Bernard
      – PersonEntity:
          Name:
            NameFull: Tang, Yuanqing
      – PersonEntity:
          Name:
            NameFull: Urwyler, Heinrich
      – PersonEntity:
          Name:
            NameFull: Wittlin, Sergio
      – PersonEntity:
          Name:
            NameFull: Charman, William N.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 19
              M: 08
              Text: 8/19/2004
              Type: published
              Y: 2004
          Identifiers:
            – Type: issn-print
              Value: 00280836
          Numbering:
            – Type: volume
              Value: 430
            – Type: issue
              Value: 7002
          Titles:
            – TitleFull: Nature
              Type: main
ResultId 1