Synthesis and antimalarial activity of pyrazolo and pyrimido benzothiazine dioxide derivatives

Arthur Barazarte, Gricela Lobo, Neira Gamboa, Juan R. Rodrigues, Mario V. Capparelli, Ángel Álvarez-Larena, Simón E. López, Jaime E. Charris

    Research output: Contribution to journalArticleResearchpeer-review

    31 Citations (Scopus)

    Abstract

    A series of phenylsubstituted pyrazolo and pyrimido benzothiazine dioxide derivatives were synthesized and investigated for their abilities to inhibit β-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent Plasmodium berghei. Compounds 3-amino-7-chloro-9-(2′-methylpheyl)-1,9-dihydro-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide 2b and 2,4-diamino-8-chloro-10H-phenyl-pyrimido-[5,4-b]benzothiazine 5,5-dioxide 3a were the most promising as inhibitors of hemoglobin hydrolysis, however, their effect as inhibitors of β-hematin formation was marginal, except for compound 3-amino-7-chloro-9-(3′-chlorophenyl)-1,9dihydro-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide 2g. The most active compound to emerge from the in vitro and in vivo murine studies was 2b, suggesting an antimalarial activity via inhibition of hemoglobin hydrolysis, however, not as efficient as chloroquine. © 2008.
    Original languageEnglish
    Pages (from-to)1303-1310
    JournalEuropean Journal of Medicinal Chemistry
    Volume44
    Issue number3
    DOIs
    Publication statusPublished - 1 Mar 2009

    Keywords

    • β-Hematin
    • Benzothiazines
    • Hemoglobin
    • Plasmodium berghei
    • Pyrazol
    • Pyrimidine

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