Thiolactomycin analogues as potential anti-Toxoplasma gondii agents

E.S. Martins-Duarte, W. de Souza, R.C. Vommaro, S.M. Jones, I.H. Gilbert, G.C. Atella

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)

    Abstract

    The discovery of new compounds active against Toxoplasma gondii is extremely important due to the severe disease caused by this pathogen in immunocompromised hosts and to congenital infection. Type II fatty acid biosynthesis has shown to be a promising target for drug intervention in toxoplasmosis. Here we describe the inhibitory effect of 8 thiolactomycin (TLM) analogues against tachyzoite-infected LLC-MK cells. The TLM analogues demonstrated anti-T. gondii activity, arresting tachyzoite proliferation with IC values in the micromolar level after 24 h and 48 h of treatment. Metabolic labelling of extracellular parasites treated with TLM analogues using [H]acetate demonstrated that these drugs affected acylglycerol synthesis. The rapid reduction of parasite load suggests that these compounds have selective cytotoxic effects against T. gondii. Transmission electron microscopy demonstrated that TLM analogues interfered with membrane-bounded organelles and parasite division and this in turn affected parasite development and survival.
    Original languageEnglish
    Pages (from-to)411-415
    Number of pages5
    JournalParasitology International
    Volume58
    Issue number4
    DOIs
    Publication statusPublished - 1 Dec 2009

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