Thiolactomycin analogues as potential anti-Toxoplasma gondii

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• 作者：Erica S. Martins-Duarte ; Simon M. Jones ; Ian H Gilbert ; Georgia C. Atella ; W ; erley de Souza ; Rossiane C. Vommaro
• 关键词：Apicomplexa ; Apicoplast ; Thiolactomycin ; Fatty acid biosynthesis
• 刊名：Parasitology International
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：58
• 期：4
• 页码：411-415
• 全文大小：758 K

文摘

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-MK₂ cells. The TLM analogues demonstrated anti-T. gondii activity, arresting tachyzoite proliferation with IC₅₀ values in the micromolar level after 24 h and 48 h of treatment. Metabolic labelling of extracellular parasites treated with TLM analogues using [³H]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.