ArticleAntimicrobial agents and chemotherapy2012
Novel N-benzoyl-2-hydroxybenzamide disrupts unique parasite secretory pathway.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
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- The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target.Bioorganic & medicinal chemistry letters · 2014Article
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- Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion.PLoS pathogens · 2013Review
- Modification of triclosan scaffold in search of improved inhibitors for enoyl-acyl carrier protein (ACP) reductase in Toxoplasma gondii.ChemMedChem · 2013Article
- Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides.Bioorganic & medicinal chemistry letters · 2013Article
- Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase.Bioorganic & medicinal chemistry letters · 2013Article
- Salicylanilide inhibitors of Toxoplasma gondii.Journal of medicinal chemistry · 2012Article
- Molecular target validation, antimicrobial delivery, and potential treatment of Toxoplasma gondii infections.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Synthesis, biological evaluation, and structure-activity relationships of N-benzoyl-2-hydroxybenzamides as agents active against P. falciparum (K1 strain), Trypanosomes, and Leishmania.Journal of medicinal chemistry · 2012Article
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Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
Abstract
Toxoplasma gondii is a protozoan parasite that can damage the human brain and eyes. There are no curative medicines. Herein, we describe our discovery of N-benzoyl-2-hydroxybenzamides as a class of compounds effective in the low nanomolar range against T. gondii in vitro and in vivo. Our lead compound, QQ-437, displays robust activity against the parasite and could be useful as a new scaffold for development of novel and improved inhibitors of T. gondii. Our genome-wide investigations reveal a specific mechanism of resistance to N-benzoyl-2-hydroxybenzamides mediated by adaptin-3β, a large protein from the secretory protein complex. N-Benzoyl-2-hydroxybenzamide-resistant clones have alterations of their secretory pathway, which traffics proteins to micronemes, rhoptries, dense granules, and acidocalcisomes/plant-like vacuole (PLVs). N-Benzoyl-2-hydroxybenzamide treatment also alters micronemes, rhoptries, the contents of dense granules, and, most markedly, acidocalcisomes/PLVs. Furthermore, QQ-437 is active against chloroquine-resistant Plasmodium falciparum. Our studies reveal a novel class of compounds that disrupts a unique secretory pathway of T. gondii, with the potential to be used as scaffolds in the search for improved compounds to treat the devastating diseases caused by apicomplexan parasites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.