University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Veterinary and Agricultural Sciences
  • Melbourne Veterinary School
  • Veterinary Biosciences
  • Veterinary Biosciences - Research Publications
  • View Item
  • Minerva Access
  • Veterinary and Agricultural Sciences
  • Melbourne Veterinary School
  • Veterinary Biosciences
  • Veterinary Biosciences - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    1-Methyl-1H-pyrazole-5-carboxamide Derivatives Exhibit Unexpected Acute Mammalian Toxicity.

    Thumbnail
    Citations
    Altmetric
    Author
    Preston, S; Garcia-Bustos, J; Hall, LG; Martin, SD; Le, TG; Kundu, A; Ghoshal, A; Nguyen, NH; Jiao, Y; Ruan, B; ...
    Date
    2021-01-14
    Source Title
    Journal of Medicinal Chemistry
    Publisher
    American Chemical Society (ACS)
    University of Melbourne Author/s
    Garcia-Bustos, Jose; Jabbar, Abdul; Gasser, Robin; Chang, Bill
    Affiliation
    Veterinary Biosciences
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Preston, S., Garcia-Bustos, J., Hall, L. G., Martin, S. D., Le, T. G., Kundu, A., Ghoshal, A., Nguyen, N. H., Jiao, Y., Ruan, B., Xue, L., Huang, F., Chang, B. C. H., McGee, S. L., Wells, T. N. C., Palmer, M. J., Jabbar, A., Gasser, R. B. & Baell, J. B. (2021). 1-Methyl-1H-pyrazole-5-carboxamide Derivatives Exhibit Unexpected Acute Mammalian Toxicity.. J Med Chem, 64 (1), pp.840-844. https://doi.org/10.1021/acs.jmedchem.0c01793.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/258570
    DOI
    10.1021/acs.jmedchem.0c01793
    Abstract
    A series of 1-methyl-1H-pyrazole-5-carboxamides were synthesized as potent inhibitors of the parasitic nematode of sheep, Haemonchus contortus. These compounds did not show overt cytotoxicity to a range of mammalian cell lines under standard in vitro culture conditions, had high selectivity indices, and were progressed to an acute toxicity study in a rodent model. Strikingly, acute toxicity was observed in mice. Experiments measuring cellular respiration showed a dose-dependent inhibition of mitochondrial respiration. Under these conditions, potent cytotoxicity was observed for these compounds in rat hepatocytes suggesting that the potent acute mammalian toxicity of this chemotype is most likely associated with respiratory inhibition. In contrast, parasite toxicity was not correlated to acute toxicity or cytotoxicity in respiring cells. This paper highlights the importance of identifying an appropriate in vitro predictor of in vivo toxicity early on in the drug discovery pipeline, in particular assessment for in vitro mitochondrial toxicity.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Veterinary Biosciences - Research Publications [441]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors