147974-20-7Relevant 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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, (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.
Lewis acid catalyzed synthesis of cyclic carbonates, precursors of 1,2- and 1,3-diols
Cornil, Johan,Gonnard, Laurine,Guerinot, Amandine,Reymond, Sebastien,Cossy, Janine
supporting information, p. 4958 - 4962 (2014/08/18)
An eco-friendly synthesis of cyclic carbonates through a Lewis acid catalyzed cyclization of tert-butyl carbonates is described. These cyclic carbonates are precursors of 1,2- and 1,3-diols, and the developed method was applied to a short synthesis of a diarylheptanoid, (3S,5S)-alpinikatin.
Design, synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity
Campos, Catherine A.,Gianino, Joseph B.,Bailey, Barbara J.,Baluyut, Mary E.,Wiek, Constanze,Hanenberg, Helmut,Shannon, Harlan E.,Pollok, Karen E.,Ashfeld, Brandon L.
supporting information, p. 6874 - 6878 (2014/01/06)
Using an innovative approach toward multiple carbon-carbon bond-formations that relies on the multifaceted catalytic properties of titanocene complexes we constructed a series of C1-C7 analogs of curcumin for evaluation as brain and peripheral nervous system anti-cancer agents. C2-Arylated analogs proved efficacious against neuroblastoma (SK-N-SH & SK-N-FI) and glioblastoma multiforme (U87MG) cell lines. Similar inhibitory activity was also evident in p53 knockdown U87MG GBM cells. Furthermore, lead compounds showed limited growth inhibition in vitro against normal primary human CD34+hematopoietic progenitor cells. Taken together, the present findings indicate that these curcumin analogs are viable lead compounds for the development of new central and peripheral nervous system cancer chemotherapeutics with the potential for little effects on normal hematopoietic progenitor cells.
Enantioselective total synthesis of (-)-ericanone
Dias, Luiz C.,Kuroishi, Paula K.,Polo, Ellen C.,De Lucca Jr., Emílio C.
, p. 980 - 982 (2013/02/25)
The first total synthesis of (-)-ericanone was achieved in 10 steps with a 16% overall yield from p-hydroxybenzaldehyde. Notable features of this stereocontrolled approach include a Keck allylation to install the stereocenter at C3 and a 1,5-anti aldol reaction to install the hydroxyl group at C7.
Pd-catalyzed arylation reactions with phenol diazonium salts: Application in the synthesis of diarylheptanoids
Schmidt, Bernd,Hoelter, Frank,Kelling, Alexandra,Schilde, Uwe
supporting information; experimental part, p. 3357 - 3365 (2011/06/28)
The first total synthesis of the natural product (3S,7R)-5,6-dehydro-de-O- methyl centrolobine and various analogues is reported, using a highly regio- and diastereoselective Mizoroki-Heck reaction of phenol diazonium salts and enantiopure dihydropyrans. The assigned relative configuration was confirmed by single-crystal X-ray structure analysis, but a revision of the absolute configuration is proposed based on polarimetric measurement.
One-Pot Bi(OTf)catalyzed oxidative deprotection of tert -butyldimethyl silyl ethers with TEMPO and co-oxidants
Barnych, Bogdan,Vatèle, Jean-Michel
experimental part, p. 2048 - 2052 (2011/10/19)
A sequential one-pot synthesis for the oxidation of primary and secondary tert-butyldimethylsilyl (TBDMS) ethers, using catalytic amounts of metal triflates and TEMPO in combination with PhIO or PhI(OAc)in THF or acetonitrile, is described. Acid-sensitive protecting groups such as methylidene, isopropylidene, acetals, and Boc are unaffected under the reaction conditions. Another feature of this procedure is its high selectivity for TBDMS ethers over tert-butyldiphenylsilyl ethers and of aliphatic TBDMS groups over phenolic TBDMS groups. Georg Thieme Verlag Stuttgart - New York.
Stereoselective total synthesis of (+)-dodoneine
Allais, Florent,Ducrot, Paul-Henri
experimental part, p. 1649 - 1653 (2010/06/20)
A total synthesis of the naturally occurring dihydropyranone dodoneine is reported. The combination of a highly catalytic enantioselective allylboration and a highly diastereoselective allylstannation was used for the stereoselective generation of the two stereogenic centers. The pyranone ring was created in two steps through generation of a Z-configured ,-unsaturated ester and lactonization via intramolecular transesterification. Georg Thieme Verlag Stuttgart.
Rationally improved chiral Bronsted acid for catalytic enantioselective allylboration of aldehydes with an expanded reagent scope
Rauniyar, Vivek,Hall, Dennis G.
supporting information; experimental part, p. 4236 - 4241 (2009/09/30)
(Chemical Equation Presented) One of the most useful reactions in organic synthesis, the stereocontrolled addition of allylic metal reagents to carbonyl compounds, provides access to enantiomerically enriched homoallylic alcohols related to the acetate, propionate, and other oxygen-containing functionalities present in a large number of biologically active natural products and pharmaceutical drugs. In the search for an ideal carbonyl allylation methodology, the catalytic enantioselective allylboration presents numerous advantages such as a high chemo-, diastereo-, and enantiocontrol with stable and nontoxic pinacol allylic boronates. This article reports a rationally improved diol·SnCl4 complex as chiral protic acid catalyst, which provides unprecedented levels of enantioselectivity in the catalytic allylation, methallylation, crotylation, and 2-bromoallylation of aliphatic aldehydes. The new diol, p-F-Vivol (4b), enables a more active diol·SnCl4 catalyst that can compete more effectively with the background uncatalyzed allylboration. The usefulness of this optimized catalytic allylboration methodology was demonstrated with an efficient synthesis of the naturally occurring pyranone (+)-dodoneine and to the preparation of biologically important exomethylene-γ-lactones.
Stereoselective synthesis of the naturally occurring 2-pyranone dodoneine
Alvarez-Bercedo, Paula,Falomir, Eva,Murga, Juan,Carda, Miguel,Marco, J. Alberto
body text, p. 4015 - 4018 (2009/04/11)
The first total synthesis of the naturally occurring dihydropyranone dodoneine is reported. Asymmetric allylation reactions were used for the stereoselective generation of the two stereogenic centers. The pyranone ring was created by ring-closing metathes
