Journal ArticleDOI
Oxidosqualene cyclase inhibitors as antimicrobial agents.
Jerald C. Hinshaw,Dae-Yeon Suh,Philippe Garnier,Frederick S. Buckner,Richard T. Eastman,Seiichi P. T. Matsuda,Bridget M. Joubert,Isabelle Coppens,Keith A. Joiner,Salim Merali,Theodore E. Nash,Glenn D. Prestwich +11 more
TLDR
A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture.Abstract:
Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens. A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture. Selectivity for the microorganisms in preference to mammalian cells was observed.read more
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Trypanocidal drugs: mechanisms, resistance and new targets
Shane R. Wilkinson,John M. Kelly +1 more
TL;DR: The properties of these drugs are reviewed, new findings on their modes of action and the mechanisms by which resistance can arise are described and how a greater understanding of parasite biology is being exploited in the search for novel chemotherapeutic agents is outlined.
Journal ArticleDOI
Ergosterol biosynthesis and drug development for Chagas disease.
TL;DR: The main putative advantages of EBI over currently available therapies include their higher potency and selectivity in both acute and chronic infections, activity against NFX and BZN-resistant T. cruzi strains, and much better tolerability and safety profiles.
Journal ArticleDOI
Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole.
Gustavo Benaim,John M. Sanders,Yael Garcia-Marchán,Claudia Colina,Renee Lira,Aura Caldera,Gilberto Payares,Cristina Sanoja,Juan M. Burgos,Annette Leon-Rossell,Juan Luis Concepcion,Alejandro G. Schijman,Mariano J. Levin,Eric Oldfield,Julio A. Urbina +14 more
TL;DR: It is found that amiodarone, in addition to disrupting the parasites' Ca( 2+) homeostasis, also blocks ergosterol biosynthesis, and that posaconazole also affects Ca(2+)Homeostasis.
Journal ArticleDOI
Trypanosoma cruzi targets for new chemotherapeutic approaches
TL;DR: There is an urgent need for better drugs to treat chagasic patients and the state of the art of drug targets against Trypanosoma cruzi is reviewed with emphasis on sterol metabolism, kinetoplast DNA sites, trypanothione reductase, cysteine proteinase, hypoxanthine–guanine phosphoribosyltransferase and glyceraldehyde-3-phosphate dehydrogenase.
References
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Book
Comprehensive natural products chemistry
TL;DR: Collecting together aspects of the chemistry of natural products, this work was conceived as a source of the underlying general principles governing modern natural products physics as discussed by the authors, and was used as a basis for the present paper.
Journal ArticleDOI
Progress in the mitsunobu reaction. a review
TL;DR: A review of progress in the MITSUNOBU this article reaction can be found in this article, with a focus on the MIT SUNOBU reaction and a review of the progress.
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Enzyme Mechanisms for Polycyclic Triterpene Formation.
TL;DR: It can be concluded that the role of the oxidosqualene cyclases involves protection of the intermediate carbocation against addition of water or deprotonation by base, thereby allowing the shift of the hydride and methyl groups along a thermodynamically and kinetically favorable cascade.
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Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa
TL;DR: Leishmania parasites can survive with greatly altered sterol profiles induced by continuous treatment with low concentrations of some inhibitors and they also have some ability to utilise and metabolise host sterol, which may permit the parasites to evade treatment with sterol biosynthesis inhibitors in some clinical situations.
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Toxoplasma gondii Exploits Host Low-Density Lipoprotein Receptor-Mediated Endocytosis for Cholesterol Acquisition
TL;DR: The obligate intracellular protozoan Toxoplasma gondii resides within a specialized parasitophorous vacuole (PV), isolated from host vesicular traffic and cholesterol trafficking to the PV is independent of the pathways involving the host Golgi or endoplasmic reticulum.