Synthesis and anthelmintic activity of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives

Vaida Milišiūnaitė, Alena Kadlecová, Asta Žukauskaitė, Karel Doležal, Miroslav Strnad, Jiří Voller, Eglė Arbačiauskienė (Corresponding author), Wolfgang Holzer, Algirdas Šačkus (Corresponding author)

    Publications: Contribution to journalArticlePeer Reviewed

    Abstract

    Abstract: A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing O-acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans. Five compounds, namely 2-phenyl[1]benzopyrano[2,3-c]pyrazol-4(2H)-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36, 38, 40 and 43, respectively, altered the development of C. elegans. While the activities of 33 and 43 were rather modest, compounds 36, 38 and 40 inhibited the growth of the worms at concentrations of approximately 1-3 µM. At these concentrations, the compounds did not kill the worms, but they strongly inhibited their development, with the majority of larvae never progressing past the L1 stage. Moreover, testing in non-cancer human cell lines showed that, with exception of 7-bromo derivative 40, the active compounds have favourable toxicity profiles. Graphic abstract: [Figure not available: see fulltext.]

    Original languageEnglish
    Pages (from-to)1025-1042
    Number of pages18
    JournalMolecular Diversity
    Volume24
    Issue number4
    DOIs
    Publication statusPublished - 1 Nov 2020

    Austrian Fields of Science 2012

    • 301207 Pharmaceutical chemistry

    Keywords

    • Anthelmintic activity
    • Benzopyrano[2,3-c]pyrazol-4(2H)-ones
    • Caenorhabditis elegans
    • Cytotoxicity
    • Pyrazole

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