Selective anti-Toxoplasma gondii activities of azasterols

Dantas-Leite, Lucas; Urbina, Julio A.; Souza, Wanderley de; Vommaro, Rossiane C.

doi:10.1016/j.ijantimicag.2003.11.005

Cited by 38 publications

(34 citation statements)

References 19 publications

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“…These include the statins (or HMG-CoA reductase inhibitors), a class of drug used to lower plasma cholesterol level, that inhibit the enzyme HMG-CoA reductase. Multiple statins have been reported to have a selective inhibitory effect on T. gondii, including simvastatin [7] and the azasterols, which are known inhibitors of 24(25)-sterol methyltransferase in protozoa and fungi [8,9]. Squalene synthase inhibitors and quinuclidine derivatives also produce anti-proliferative effects [17].…”

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confidence: 99%

Host Cholesterol Synthesis Contributes to Growth of Intracellular Toxoplasma gondii in Macrophages

Nishikawa

Ibrahim

Kameyama

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. The intracellular protozoan Toxoplasma gondii lacks the ability to synthesize sterol and scavenges cholesterol from the lowdensity lipoprotein receptor (LDLR) pathway of its host to facilitate replication. Sterol biosynthesis inhibitors, however, have a demonstrated anti-Toxoplasma effect. In this study, we examined the host mevalonate pathway as a novel source of cholesterol for T. gondii and its effects on parasite growth in macrophages. Parasite growth did not significantly change in the absence of LDLR or when LDL was exogenously supplemented. Lovastatin and compactin, both inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase in the mevalonate pathway, significantly inhibited T. gondii growth in both wild-type and LDLR-knockout macrophages. Parasite growth was also suppressed by squalestatin, an inhibitor of squalene synthase, despite mevalonate producing isoprenoid intermediates in host cells. The present study demonstrates that lovastatin, compactin and squalestatin have anti-Toxoplasma activities and that the host cholesterol synthesis may contribute to parasite growth in macrophages.

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confidence: 99%

Host Cholesterol Synthesis Contributes to Growth of Intracellular Toxoplasma gondii in Macrophages

Nishikawa

Ibrahim

Kameyama

et al. 2011

The Journal of Veterinary Medical Science

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“…For instance, pyridinylimidazole and imidazopyrimidine, inhibitors of human p38 mitogen-activated protein kinase, caused inhibition of the parasite replication in HFF cells and prevented animals from fatal infection [47]. Similar activity was shown by azasterols known as D24(25)-sterol methyltransferase inhibitors which in in vitro studies inhibited parasite growth and contributed to changes in the ultrastructure of the protozoan [48]. Furthermore, inhibitors of mammalian squalene synthase reduced the parasite proliferation rate, which was accompanied by changes of morphological structure of T. gondii tachyzoites [49].…”

Section: Inhibitors Of Human Enzymesmentioning

confidence: 84%

Human toxoplasmosis–Searching for novel chemotherapeutics

Antczak

Dzitko

Długońska

2016

Biomedicine & Pharmacotherapy

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“…Other reports on lanosterol derivatives with amine functionality in the side chain to assess their potency as anti-fungal agents have been described. [35][36][37][38] The majority of research has documented strong antifungal activity in vitro with C-3 and C-24 derivatives.…”

Section: Introductionmentioning

confidence: 99%