A fluorinated phenylbenzothiazole arrests the trypanosoma cruzi cell cycle and diminishes the infection of mammalian host cells

Roberto I. Cuevas-Hernández, Richard M.B.M. Girard, Sarai Martínez-Cerón, Marcelo Santos Da Silva, Maria Carolina Elias, Marcell Crispim, José G. Trujillo-Ferrara, Ariel Mariano Silber

    Research output: Contribution to journalArticle

    Abstract

    Chagas disease (CD) is a human infection caused by Trypanosoma cruzi. CD was traditionally endemic to the Americas; however, due to migration it has spread to countries where it is not endemic. The current chemotherapy to treat CD induces several side effects, and its effectiveness in the chronic phase of the disease is controversial. In this contribution, substituted phenylbenzothiazole derivatives were synthesized and biologically evaluated as trypanocidal agents against Trypanosoma cruzi. The trypanocidal activities of the most promising compounds were determined through systematic in vitro screening, and their modes of action were determined as well. The physicochemical-structural characteristics responsible for the trypanocidal effects were identified, and their possible therapeutic application in Chagas disease is discussed. Our results show that the fluorinated compound 2-methoxy-4-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl] phenol (BT10) has the ability to inhibit the proliferation of epimastigotes [IC50(Epi) 23.11.75] and intracellular forms of trypomastigotes [IC50(Tryp) 8.52.9M] and diminishes the infection index by more than 80%. In addition, BT10 has the ability to selectively fragment 68% of the kinetoplastid DNA compared with 5% of nucleus DNA. The mode of action for BT10 on T. cruzi suggests that the development of fluorinated phenylbenzothiazole with electron-withdrawing substituent is a promising strategy for the design of trypanocidal drugs.

    Original languageEnglish
    Article numbere01742
    JournalAntimicrobial Agents and Chemotherapy
    Volume64
    Issue number2
    DOIs
    StatePublished - 27 Jan 2020

    Keywords

    • Antiparasitic agents
    • Chemotherapy
    • kDNA
    • Phenylbenzothiazole
    • Trypanosoma cruzi

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