scholarly journals Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

2013 ◽  
Vol 9 ◽  
pp. 215-222 ◽  
Author(s):  
Francesca Pertici ◽  
Norbert Varga ◽  
Arnoud van Duijn ◽  
Matias Rey-Carrizo ◽  
Anna Bernardi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Sonogashira Reaction ◽  
Phenylene Ethynylene ◽  
Efficient Synthesis ◽  
Inhibitory Potency ◽  
Silyl Group ◽  
Rigid Spacer ◽  
Inhibition Studies

The synthesis of phenylene-ethynylene rods and their use as rigid spacers is described. Alternation of a Sonogashira reaction and silyl group cleavage was used to obtain rigid spacers with even and odd numbers of phenylene units. Preliminary applications of these rods in divalent systems are shown. Inhibition studies with Pseudomonas Aeruginosa lectin LecA showed that the rigid spacer proved greatly beneficial for the inhibitory potency.

An Efficient Synthesis of the Pentasaccharide Repeating Unit of Pseudomonas aeruginosa Psl Exopolysaccharide

Synlett ◽  
2019 ◽  
Vol 31 (05) ◽  
pp. 469-474 ◽  
Author(s):  
Fruzsina Demeter ◽  
Margaret Dah-Tsyr Chang ◽  
Yuan-Chuan Lee ◽  
Anikó Borbás ◽  
Mihály Herczeg
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Coupling Reaction ◽  
Building Blocks ◽  
Bacterial Biofilm ◽  
Efficient Synthesis ◽  
Negative Bacterium ◽  
Resistant Species ◽  
Promising Therapeutic Target ◽  
Polysaccharide Synthesis ◽  
Life Threatening

Pseudomonas aeruginosa is a biofilm-forming Gram-negative bacterium and a leading cause of life-threatening nosocomial infections. The polysaccharide synthesis locus (Psl) exopolysaccharide of P. aeruginosa is a key constituent of the defending bacterial biofilm layer and is a promising therapeutic target for resistant species. The Psl exopolysaccharide is built up from repeating pentasaccharide units which contain one α- and two β-mannosidic linkages, and one l-rhamnose and one d-glucose moieties. The preparation of this pentasaccharide was first described by Boons et al. in a 34-step synthesis. Based on their work, we have developed a new and effective pathway for the synthesis of the repeating pentasaccharide unit of the Psl exopolysaccharide. We have succeeded in simplifying the synthesis of the l-rhamnose and the α-selective d-mannose building blocks. Furthermore, taking advantage of a chemoselective pre-activation-based β-mannosylation, we directly prepare a thioglycoside disaccharide donor and use it in the next coupling reaction without further transformation. The pentasaccharide, in the form of a p-methoxyphenyl glycoside, is prepared in 26 steps, which is suitable for biological testing.

The efficient synthesis and simple resolution of a prolineboronate ester suitable for enzyme-inhibition studies

Tetrahedron ◽  
1993 ◽  
Vol 49 (5) ◽  
pp. 1009-1016 ◽  
Author(s):  
Terence A. Kelly ◽  
Victor U. Fuchs ◽  
Clark W. Perry ◽  
Roger J. Snow
Keyword(s):  
Enzyme Inhibition ◽  
Efficient Synthesis ◽  
Inhibition Studies

scholarly journals Two Forms of Tyrosyl-tRNA Synthetase from Pseudomonas aeruginosa: Characterization and Discovery of Inhibitory Compounds

2020 ◽  
Vol 25 (9) ◽  
pp. 1072-1086
Author(s):  
Casey A. Hughes ◽  
Varesh Gorabi ◽  
Yaritza Escamilla ◽  
Frank B. Dean ◽  
James M. Bullard
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Trna Synthetase ◽  
Gram Negative Bacteria ◽  
Compound Library ◽  
Mechanism Of Inhibition ◽  
Inhibitory Compounds ◽  
Human Cell Cultures ◽  
Inhibition Studies ◽  
Substrate Competition

Pseudomonas aeruginosa is a multidrug-resistant (MDR) pathogen and a causative agent of both nosocomial and community-acquired infections. The genes ( tyrS and tyrZ) encoding both forms of P. aeruginosa tyrosyl-tRNA synthetase (TyrRS-S and TyrRS-Z) were cloned and the resulting proteins purified. TyrRS-S and TyrRS-Z were kinetically evaluated and the Km values for interaction with Tyr, ATP, and tRNATyr were 172, 204, and 1.5 μM and 29, 496, and 1.9 μM, respectively. The kcatobs values for interaction with Tyr, ATP, and tRNATyr were calculated to be 3.8, 1.0, and 0.2 s−1 and 3.1, 3.8, and 1.9 s−1, respectively. Using scintillation proximity assay (SPA) technology, a druglike 2000-compound library was screened to identify inhibitors of the enzymes. Four compounds (BCD37H06, BCD38C11, BCD49D09, and BCD54B04) were identified with inhibitory activity against TyrRS-S. BCD38C11 also inhibited TyrRS-Z. The IC50 values for BCD37H06, BCD38C11, BCD49D09, and BCD54B04 against TyrRS-S were 24, 71, 65, and 50 μM, respectively, while the IC50 value for BCD38C11 against TyrRS-Z was 241 μM. Minimum inhibitory concentrations (MICs) were determined against a panel of clinically important pathogens. All four compounds were observed to inhibit the growth of cultures of both Gram-positive and Gram-negative bacteria organisms with a bacteriostatic mode of action. When tested against human cell cultures, none of the compounds were toxic at concentrations up to 400 μg/mL. In mechanism of inhibition studies, BCD38C11 and BCD49D09 selectively inhibited TyrRS activity by competing with ATP for binding. BCD37H06 and BCD54B04 inhibited TyrRS activity by a mechanism other than substrate competition.

Alkyne-Substituted Fimbrolide Analogues as Novel Bacterial Quorum-Sensing Inhibitors

2018 ◽  
Vol 71 (9) ◽  
pp. 708 ◽  
Author(s):  
Nripendra Nath Biswas ◽  
George M. Iskander ◽  
Marcin Mielczarek ◽  
Tsz Tin Yu ◽  
David StC Black ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Cell Communication ◽  
Social Adaptation ◽  
Sonogashira Reaction ◽  
Coupling Reactions ◽  
Bacterial Quorum Sensing ◽  
Bacterial Quorum ◽  
High Yields ◽  
Brominated Furanones

Gram-negative bacteria such as Pseudomonas aeruginosa use furanosyl diesters as autoinducers for quorum sensing (QS), a major regulatory and cell-to-cell communication system for social adaptation, virulence factor production, biofilm formation, and antibiotic resistance. A range of natural and synthetic brominated furanones, i.e. fimbrolide derivatives, have been found to act as inhibitors of QS-dependent bacterial phenotypes, complementing the bactericidal ability of traditional antibiotics. In this work, several novel acetylene analogues of fimbrolides were synthesised in moderate to high yields via Sonogashira coupling reactions of brominated furanones 4-bromo-5-(bromomethylene)furan-2(5H)-one 4 and 5-(dibromomethylene)-3-ethylfuran-2(5H)-one 5. The Sonogashira reaction of acetylenes on 4-bromo-5-(bromomethylene)furan-2(5H)-one 4 was favoured at the C5 methylene bromide over the C4 bromide substituent. On biological testing, the most potent compounds 13 and 14 showed 82 and 98 % bacterial quorum-sensing inhibitory (QSI) activity against Pseudomonas aeruginosa reporter strain respectively.

Structure and inhibition studies of a type II beta-carbonic anhydrase psCA3 from Pseudomonas aeruginosa

2015 ◽  
Vol 23 (15) ◽  
pp. 4831-4838 ◽  
Author(s):  
Melissa A. Pinard ◽  
Shalaka R. Lotlikar ◽  
Christopher D. Boone ◽  
Daniela Vullo ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Carbonic Anhydrase ◽  
Type Ii ◽  
Beta Carbonic Anhydrase ◽  
Inhibition Studies

An acetylene zipper—Sonogashira reaction sequence for the efficient synthesis of conjugated arylalkadiynols

2013 ◽  
Vol 54 (18) ◽  
pp. 2235-2238 ◽  
Author(s):  
Alexandra E. Kulyashova ◽  
Viktor N. Sorokoumov ◽  
Vladimir V. Popik ◽  
Irina A. Balova
Keyword(s):  
Sonogashira Reaction ◽  
Efficient Synthesis ◽  
Reaction Sequence

ChemInform Abstract: An Acetylene Zipper-Sonogashira Reaction Sequence for the Efficient Synthesis of Conjugated Arylalkadiynols.

ChemInform ◽  
2013 ◽  
Vol 44 (32) ◽  
pp. no-no
Author(s):  
Alexandra E. Kulyashova ◽  
Viktor N. Sorokoumov ◽  
Vladimir V. Popik ◽  
Irina A. Balova
Keyword(s):  
Sonogashira Reaction ◽  
Efficient Synthesis ◽  
Reaction Sequence
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