Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• analogues was observed to inhibit production of the virulence factor pyocyanin in the human pathogen Pseudomonas aeruginosa, which may be a result of their similarity to the Pseudomonas quinolone signal (PQS) quorum sensing autoinducer. This provided new insights regarding the effect of N-substitution in

• -position, there is a structural resemblance to the Pseudomonas quinolone signal (PQS), and its biosynthetic precursor 2-heptyl-4(1H)-quinolone (HHQ), which are vital to the cooperative behaviour of the human pathogen Pseudomonas aeruginosa via quorum sensing (QS). This is a means by which bacteria alter

• in quorum sensing signalling by the human pathogen Pseudomonas aeruginosa, and 2-heptyl-4(1H)-quinolone (HHQ), the biosynthetic precursor of PQS. Growth of E. coli ESS with time in the presence of 200 μM of each compound. A) Natural product series. B) Saturated analogue series. C) Truncated analogue

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• tumefaciens [45][51][52][53][54]; AbaR from Acinetobacter baumannii [47][55]; LasR [45][51][52][53][54][56], QscR [57], and RhlR [48][56] from Pseudomonas aeruginosa; ExpR1 and ExpR2 from Pectobacterium carotovora [46][58]; and LuxR from Vibrio fischeri [45][51][52][53][54]. The full set of 151 compounds

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• , 66123 Saarbrücken, Germany German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Saarbrücken, Germany 10.3762/bjoc.14.241 Abstract The Gram-negative opportunistic pathogen Pseudomonas aeruginosa causes severe nosocomial infections. It uses quorum sensing (QS) to regulate and

• highlights the published drug discovery efforts providing insights into the compound binding modes if available. Furthermore, suitability of the individual targets for pathoblocker design is discussed. Keywords: anti-infectives; pathoblockers; PQS; Pseudomonas aeruginosa; quorum sensing; Introduction In

• bactericidal or bacteriostatic effects, but mediate their effect through pathogen-specific action on virulence mechanisms, has been unveiled. This short review focuses on the current knowledge of one particular antivirulence strategy against the important pathogen Pseudomonas aeruginosa, which is based on the

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• pathogens, [4] Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species, were initially identified as the most problematic ones. In 2017, an extended list of twelve pathogens, currently considered as those with the highest

• FmlH (compounds 8 and 9) and Pseudomonas aeruginosa LecA (compounds 10–12). Mannosides and fucosides as inhibitors of P. aeruginosa LecB. β-Cyclodextrin-based antitoxin 19 against S. aureus α-hemolysin and the decavalent Shiga toxin inhibitors STARFISH (20) and DAISY (21). The mechanism of quorum

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• of Agronomical Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Bucharest, Romania Institute of Cellular Biology and Pathology Nicolae Simionescu of Romanian Academy, Romania 10.3762/bjoc.14.235 Abstract Pseudomonas aeruginosa relies on the quorum sensing (QS) signaling system as a

• . Pseudomonas aeruginosa is recognized as the principal pathogen responsible of high morbidity and mortality in patients with cystic fibrosis, one of the most common life-threatening autosomal recessive genetic disease in Northwest European populations, determined by mutations in the cystic fibrosis

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• modulators against a multitude of Gram-negative bacterial species, including Pseudomonas aeruginosa, Vibrio fischeri, Vibrio harveyi, Vibrio cholerae, and Acinetobacter baumannii has been conducted [6][7][8][9][10]. Contrary, with the exception of the accessory gene regulator (agr) QS circuitry in

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• Pseudomonas aeruginosa. A series of chemoecological studies of P. aeruginosa has uncovered multifunctional roles of this quinolone class as antibacterial, antifungal, iron-chelating, and autoinducer agents to assist the survival of the producing organisms [32]. Additionally, drug discovery attempts have

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• could facilitate DNA cleavage. Moreover, these complexes showed improved biocidal activity than the free ligands against various bacterial strains such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and Klebsiella pneumonia. Nair et al. synthesized and

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• resistance genes) and the emergence of multidrug resistant strains [59]. In addition, extracellular DNA has been shown to be important for biofilm establishment and maintenance by pathogenic bacteria, such as Pseudomonas aeruginosa and Staphylococcus aureus [60][61][62]. Some other bacteria, such as E. coli

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• glycosides on mammalian cell surfaces. After this initial contact, they can infect host cells and form biofilms, both of which are key factors for their survival [9][27][28]. Examples of such opportunistic bacterial species binding to mannosides on host cells include Pseudomonas aeruginosa with its membrane

• additional hydroxy group would not contribute the maximum penalty associated with an isolated one. The cost of desolvating calcium ions (Figure 5). Opportunistic bacteria such as Pseudomonas aeruginosa or Burkholderia cenocepacia have incorporated a second calcium ion into their binding site, coordinating

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• performed as previously described [27]. The test organisms included Bacillus subtilis ATCC 6633, Staphylococcus aureus SG 511, Mycobacterium vaccae IMET 10670, Escherichia coli SG 458, Pseudomonas aeruginosa K 799/61, Sporobolomyces salmonicolor SBUG 549, Candida albicans ATCC 14053 and Penicillium notatum

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• not been studied yet, were examined as an amine component in Ugi-4CR and GBB-3CR. The generated compounds were screened for their biological activity towards Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Results and Discussion Since aminoazoles contain an

• -positive) and Escherichia coli (strain 1257), Pseudomonas aeruginosa (strain 1111) (Gram-negative). As it follows from the results obtained several of the substances studied inhibit the growth of test-microorganisms demonstrating a weak antimicrobial effect (Table 7). Generally, the compounds were found to

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• glycans in pathogens or parasites, numerous other lectins recognize such O-alkylated ligands, e.g., the pilus adhesin from Pseudomonas aeruginosa PAK [31] or PapG from Escherichia coli [32]. In contrast, methylation of lectin ligands can also prevent binding, as observed with O-methylated fucose and

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• Michaela Prothiwa David Szamosvari Sandra Glasmacher Thomas Bottcher Department of Chemistry, Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany 10.3762/bjoc.12.277 Abstract The human pathogen Pseudomonas aeruginosa uses the pqs quorum sensing system to

• for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme. Keywords: activity-based probes; PqsD; protein labelling; Pseudomonas aeruginosa; quinolones; Introduction The emergence of multi-drug resistant

• bacterial strains urges the rapid discovery of new antibiotics and the development of novel antiinfective strategies [1]. One of the leading causes for nosocomial infections is the opportunistic human pathogen Pseudomonas aeruginosa, which, by chronic infections, also poses a major threat for cystic

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• , UK Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore 138671 10.3762/bjoc.12.137 Abstract Pyocyanin is a small molecule produced by Pseudomonas aeruginosa that plays a crucial role in the pathogenesis of infections by this notorious opportunistic pathogen. The inhibition

• pathogenicity of P. aeruginosa and there is a wide range of other potential applications where the inhibition of quorum sensing is desirable. Keywords: antibacterial; antivirulence; Pseudomonas aeruginosa; pyocyanin; quorum sensing; Findings The Gram-negative bacterium Pseudomonas aeruginosa is a clinically

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• of Trichophyton mentagrophytes (MIC 6.2 µg/mL) and Epidermophyton floccosum (MIC 1.6 µg/mL) [87]. Though no activity was observed against the gram negative bacteria Escherichia coli and Pseudomonas aeruginosa, meridine (56) significantly inhibited the growth of the gram positive bacteria Bacillus

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• inhibitory activity against the Gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa. In contrast, almost all the tested N-alkyl saponins were found to inhibit the growth of the Gram-positive bacteria (Table 2). Among the

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• -hydroxybenzoate, benzyl alcohol, 2-phenoxyethanol) [45]. The authors established a clear relationship between the binding constants and the antimicrobial activity of the preservatives on various strains: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and C. albicans. Indeed, highly water-soluble

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• , inhibition of bacterial QS was recently demonstrated by a set of electrophilic probes (which included halogenated analogues of AHLs) that could covalently bind in the LasR binding pocket of Pseudomonas aeruginosa [15]. Therefore, designing analogues with small reactive moieties, such as halogenated carbon

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• glycoclusters based on a triazine core bearing D-galactose and L-fucose epitopes are able to inhibit biofilm formation by Pseudomonas aeruginosa. These multivalent ligands are simple to synthesize, are highly soluble, and can be either homofunctional or heterofunctional. The galactose-decorated cluster shows

• good affinity for Pseudomonas aeruginosa lectin lecA. They are convenient biological probes for investigating the roles of lecA and lecB in biofilm formation. Keywords: antibiotic; biofilm; glycocluster; lectin; multivalency effect; multivalent glycosystems; Introduction Pseudomonas aeruginosa (PA

• . The 6-deoxymannose isostere 15 was not tested, in view of the low affinity of the β-fucose epitopes. These clusters thus represent a readily accessible, highly soluble, and convenient tool for the investigation of the role of lecA and lecB in the formation of biofilms by Pseudomonas aeruginosa

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• efficient multivalent ligands for a series of pathological lectins. For instance, cholera toxin is bound rather efficiently by calix[4]arene [16] and calix[5]arene [17] derivatives, while examples of Pseudomonas aeruginosa LecB binding were reported with galactosylcalixarenes blocked in different

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• lectins such as ConA [43] and the LecA lectin from Pseudomonas aeruginosa [17]. With these closely related families of mannosylated dendrimers in hand, together with their known relative size in solution, we are now well positioned to evaluate their binding behavior against their cognate proteins and this