- Development of Selective Steroid Inhibitors for the Glucose-6-phosphate Dehydrogenase from Trypanosoma cruzi
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Chagas disease is a parasitic infection affecting millions of people across Latin America, imposing a dramatic socioeconomic burden. Despite the availability of drugs, nifurtimox and benznidazole, lack of efficacy and incidence of side-effects prompt the identification of novel, efficient, and affordable drug candidates. To address this issue, one strategy could be probing the susceptibility of Trypanosoma parasites toward NADP-dependent enzyme inhibitors. Recently, steroids of the androstane group have been described as highly potent but nonselective inhibitors of parasitic glucose-6-phosphate dehydrogenase (G6PDH). In order to promote selectivity, we have synthesized and evaluated 26 steroid derivatives of epiandrosterone in enzymatic assays, whereby 17 compounds were shown to display moderate to high selectivity for T. cruzi over the human G6PDH. In addition, three compounds were effective in killing intracellular T. cruzi forms infecting rat cardiomyocytes. Altogether, this study provides new SAR data around G6PDH and further supports this target for treating Chagas disease.
- Fredo Naciuk, Fabrício,Do Nascimento Faria, Jéssica,Gonc?lves Eufrásio, Amanda,Torres Cordeiro, Artur,Bruder, Marjorie
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supporting information
p. 1250 - 1256
(2020/07/27)
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- COMPOUNDS AND METHODS FOR TREATING NEOPLASIA
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The invention features compounds, pharmaceutical compositions and methods useful for the treatment of neoplasia. In particular embodiments, the compounds of the invention are useful for the treatment of multidrug resistant neoplasia.
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Page/Page column 80
(2012/02/13)
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- Effect of acid catalysis on the direct electrophilic fluorination of ketones, ketals, and enamides using Selectfluor
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The fluorination of ketones, ketals, and enamides has been achieved using the electrophilic fluorinating reagent Selectfluor (F-TEDA-BF 4). For the reactions of ketones and ketals the use of sulfuric acid (0.1 equiv) as an additive was found to facilitate the reaction leading to more rapid product formation. This behavior is analogous to the known effects of acid catalysis on the bromination of ketones. The reactions were generally quite selective leading to the formation of monofluorinated products, and could be accomplished on reaction scales up to 85 mmol using N-protected piperidone based substrates. Reactions in the presence of MeOH led to the formation of the corresponding fluoroketones or fluoroketals depending upon the substrate. The formation of the fluoroketals in this manner, as well as the fluorination of cyclic enamides are examples of multi-component coupling reactions.
- Liu, Jack,Chan, Johann,Bryant, Craig M.,Duspara, Petar A.,Lee, Ernest E.,Powell, David,Yang, Hua,Liu, Ziping,Walpole, Chris,Roberts, Edward,Batey, Robert A.
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experimental part
p. 2971 - 2975
(2012/07/28)
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- Compounds useful for treating hypertriglyceridemia
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The present invention is directed to a method for treating a patient having hypertriglyceridemia comprising administering thereto a compound of the formula:
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- Direct α-fluorination of ketones using N-F reagents
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The use of 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Accufluor NFTh) as a fluorine atom transfer reagent and methanol as solvent enabled direct regiospecific fluorofunctionalization of the α-carbonyl position in ketones w
- Stavber, Stojan,Jereb, Marjan,Zupan, Marko
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p. 2609 - 2615
(2007/10/03)
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- 5 α-pregnan-20-ones and 5-pregnen-20-ones and related compounds
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Compounds of the formulae: STR1 useful as anti-obesity, anti-diabetic, anti-coronary and hypolipidemic agents.
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- 16-substituted androstanes and 16-substituted androstenes
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Compounds of the formula: STR1 are useful as anti-cancer, anti-obesity, anti-diabetic, anti-coronary agents, anti-aging agents, anti-hypolipidemic agents and anti-autoimmune agents.
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- Homoandrostan-17-one and homoandrosten-17-ones
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Compounds of the formula: STR1 useful as anti-cancer agents, anti-obesity agents, anti-hyperglycemic agents, anti-aging agents, anti-hyperglycemic agents and anti-autoimmune agents.
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- 17-Hydroxy-steroids
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Compounds of the formulae: STR1 are useful as anti-cancer, anti-obesity, anti-diabetic, anti-coronary agents, anti-aging agents, anti-hypolipidemic agents and anti-autoimmune agents.
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