title: Sterculic Acid and Its Analogues Are Potent Inhibitors of Toxoplasma gondii.
abstract: Toxoplasmosis is a serious disease caused by Toxoplasma gondii, one of the most widespread parasites in the world. Lipid metabolism is important in the intracellular stage of T. gondii. Stearoyl-CoA desaturase (SCD), a key enzyme for the synthesis of unsaturated fatty acid is predicted to exist in T. gondii. Sterculic acid has been shown to specifically inhibit SCD activity. Here, we examined whether sterculic acid and its methyl ester analogues exhibit anti-T. gondii effects in vitro. T. gondii-infected Vero cells were disintegrated at 36 hr because of the propagation and egress of intracellular tachyzoites. All test compounds inhibited tachyzoite propagation and egress, reducing the number of ruptured Vero cells by the parasites. Sterculic acid and the methyl esters also inhibited replication of intracellular tachyzoites in HFF cells. Among the test compounds, sterculic acid showed the most potent activity against T. gondii, with an EC50 value of 36.2 μM, compared with EC50 values of 248-428 μM for the methyl esters. Our study demonstrated that sterculic acid and its analogues are effective in inhibition of T. gondii growth in vitro, suggesting that these compounds or analogues targeting SCD could be effective agents for the treatment of toxoplasmosis.
authors.affiliation: National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Hao
authors.affiliation: School of Chemistry, Bangor University, Bangor, UK.
authors.forename: Intisar Q M
authors.initials: IQ
authors.lastname: Alaraj
authors.affiliation: School of Chemistry, Bangor University, Bangor, UK.
authors.forename: Juma'a R Al
authors.initials: JR
authors.lastname: Dulayymi
authors.affiliation: School of Chemistry, Bangor University, Bangor, UK.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baird
authors.affiliation: National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003521:Cyclopropanes / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D006801:Humans; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors*; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development; D014123:Toxoplasmosis / Q000188:drug therapy* / Q000469:parasitology; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D003521:Cyclopropanes; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D013230:Stearoyl-CoA Desaturase; C003345:sterculic acid
keywords: Toxoplasma gondii; anti-Toxoplasma gondii effect; stearoyl-CoA desaturase; sterculic acid