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(2) cells. The TLM analogues demonstrated anti-T. gondii activity, arresting tachyzoite proliferation with IC(50) values in the micromolar level after 24 h and 48 h of treatment. Metabolic labelling of extracellular parasites treated with TLM analogues using [(3)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.
journal_name
Parasitol Intjournal_title
Parasitology internationalauthors
Martins-Duarte ES,Jones SM,Gilbert IH,Atella GC,de Souza W,Vommaro RCdoi
10.1016/j.parint.2009.08.004subject
Has Abstractpub_date
2009-12-01 00:00:00pages
411-5issue
4eissn
1383-5769issn
1873-0329pii
S1383-5769(09)00103-2journal_volume
58pub_type
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