939017-87-5Relevant academic research and scientific papers
Small Molecule Inhibitors of the BfrB-Bfd Interaction Decrease Pseudomonas aeruginosa Fitness and Potentiate Fluoroquinolone Activity
Hewage, Achala N. D. Punchi,Yao, Huili,Nammalwar, Baskar,Gnanasekaran, Krishna Kumar,Lovell, Scott,Bunce, Richard A.,Eshelman, Kate,Phaniraj, Sahishna M.,Lee, Molly M.,Peterson, Blake R.,Battaile, Kevin P.,Reitz, Allen B.,Rivera, Mario
, p. 8171 - 8184 (2019/06/13)
The iron storage protein bacterioferritin (BfrB) is central to bacterial iron homeostasis. The mobilization of iron from BfrB, which requires binding by a cognate ferredoxin (Bfd), is essential to the regulation of cytosolic iron levels in P. aeruginosa. This paper describes the structure-guided development of small molecule inhibitors of the BfrB-Bfd protein-protein interaction. The process was initiated by screening a fragment library and followed by obtaining the structure of a fragment hit bound to BfrB. The structural insights were used to develop a series of 4-(benzylamino)- A nd 4-((3-phenylpropyl)amino)-isoindoline-1,3-dione analogs that selectively bind BfrB at the Bfd binding site. Challenging P. aeruginosa cells with the 4-substituted isoindoline analogs revealed a dose-dependent growth phenotype. Further investigation determined that the analogs elicit a pyoverdin hyperproduction phenotype that is consistent with blockade of the BfrB-Bfd interaction and ensuing irreversible accumulation of iron in BfrB, with concomitant depletion of iron in the cytosol. The irreversible accumulation of iron in BfrB prompted by the 4-substituted isoindoline analogs was confirmed by visualization of BfrB-iron in P. aeruginosa cell lysates separated on native PAGE gels and stained for iron with Ferene S. Challenging P. aeruginosa cultures with a combination of commercial fluoroquinolone and our isoindoline analogs results in significantly lower cell survival relative to treatment with either antibiotic or analog alone. Collectively, these findings furnish proof of concept for the usefulness of small molecule probes designed to dysregulate bacterial iron homeostasis by targeting a protein-protein interaction pivotal for iron storage in the bacterial cell.
SMALL MOLECULE INHIBITORS OF THE BFRB:BFD INTERACTION
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Paragraph 0192, (2020/07/05)
The present technology provides compounds of Formula I and related methods for treating a bacterial infection as well as methods for inhibiting interaction of a bacterioferritin and a bacterioferritin-associated ferredoxin.
Phenolate-induced intramolecular ring-opening cyclization of: N -tosylaziridines: Access to functionalized benzoxacycles
Devi, Runjun,Das, Jonali,Sarma, Bipul,Das, Sajal Kumar
, p. 5846 - 5858 (2018/08/22)
Phenolate-induced, diastereo- and regioselective intramolecular exo-tet ring-opening cyclization of N-tosylaziridines has been achieved for the first time. The N-tosylaziridine substrates bearing a tethered (ortho-(tert-butyldimethylsiloxy))aryl substitue
Enantioselective Iridium-Catalyzed Allylic Cyclizations
Schafroth, Michael A.,Rummelt, Stephan M.,Sarlah, David,Carreira, Erick M.
supporting information, p. 3235 - 3238 (2017/06/23)
A method for the enantioselective synthesis of carbo- and heterocyclic ring systems enabled through the combination of Lewis acid activation and iridium-catalyzed allylic substitution is described. The reaction proceeds with branched, allylic alcohols and carbon nucleophiles as well as heteronucleophiles to give a diverse set of ring systems in good yields and with high enantioselectivities. The utility of the method is highlighted by the asymmetric syntheses of erythrococcamides A and B.
Asymmetric Pd-Catalyzed Alkene Carboamination Reactions for the Synthesis of 2-Aminoindane Derivatives
White, Derick R.,Hutt, Johnathon T.,Wolfe, John P.
, p. 11246 - 11249 (2015/09/21)
A new type of Pd-catalyzed alkene carboamination reaction that provides direct access to enantioenriched 2-aminoindanes from 2-allylphenyltriflate derivatives and aliphatic amines is described. A catalyst generated in situ from Pd(OAc)2 and (S)-tert-butylPHOX provides the functionalized carbocycles in good yield with up to >99:1 er. The transformations occur via a key anti-aminopalladation that involves intermolecular attack of an amine nucleophile on an arylpalladium alkene complex.
INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Page/Page column 40, (2014/10/18)
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. Formule (I)
INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Page/Page column 75, (2014/10/15)
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Page/Page column 62, (2014/10/15)
The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
Efficient synthesis of optically active gallocatechin-3-gallate derivatives via 6-endo-cyclization
Hirooka, Yasuo,Nitta, Mariko,Furuta, Takumi,Kan, Toshiyuki
scheme or table, p. 3234 - 3238 (2009/06/18)
Optically active dihydrobenzopyran derivatives are synthesized by 6-endo cyclization of corresponding epoxy-phenol, which is readily derived from the enantioselective epoxidation of 1,3-diarylpropene. Synthetic dihydrobenzopyrans are converted into (-)-5,7-dideoxy-gallocatechin gallate as well as (-)-5,7-dideoxy-epigallocatechin derivative. Georg Thieme Verlag Stuttgart.
Stereoselective syntheses of the 2-isopropenyl-2,3-dihydrobenzofuran nucleus: Potential chiral building blocks for the syntheses of tremetone, hydroxytremetone, and rotenone
Pelly, Stephen C.,Govender, Sameshnee,Fernandes, Manuel A.,Schmalz, Hans-Guenther,De Koning, Charles B.
, p. 2857 - 2864 (2008/02/01)
(Chemical Equation Presented) The first enantioselective synthesis of the 2-isopropenyl-2,3-dihydrobenzofuran skeleton of tremetone and hydroxytremetone from (E)-4-(2-hydroxyphenyl)-2-methyl-2-butenyl methyl carbonate and (E)-4-(2,6-dihydroxyphenyl)-2-met
