The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• antibacterial agents. Keywords: NDH-2; phenothiazine; siderophore; siderophore–antibiotic; siderophore conjugate; Introduction One of the biggest challenges facing the modern society is antibiotic resistance and the prospect of current antibiotics becoming near redundant against previously treatable

• infections [1]. To meet this challenge there is a desperate need for new antibiotics, antibiotic targets and strategies to enhance the efficacy of current antibiotics [2]. One novel strategy which is receiving significant interest is the manipulation of bacterial iron transport pathways to deliver

• antibiotics to the bacterial cell [3]. Iron is essential for bacterial survival and bacteria secrete high affinity iron chelating molecules to scavenge and solubilise Fe3+ from the extracellular environment [3]. The siderophore–Fe complex is recognised by specific receptor proteins on the outer membrane of

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

• resist antibiotic treatment via several mechanisms. First and foremost, it possesses an intrinsic resistance to many antibiotics because of the low permeability of its cell wall and due to the action of a number of efflux pumps as well as β-lactamases. Efflux pumps in particular are nifty molecular

• machineries consisting of several protein components, which in total span from the inner to the outer side of the cell membrane. Their function is to expel a wide range of xenobiotics, among them antibiotics from the cephalosporin, carbapenem, fluroquinolone and aminoglycoside classes [13]. Through this

• strains. Hence, these antibiotic-inactivating enzymes provide resistance against penicillins and cephalosporins [14]. In addition to these intrinsic capabilities, P. aeruginosa is able to acquire resistances toward antibiotics it has come in contact with. These acquired resistances can be the result of

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

• current trends continue. To avoid this scenario, new classes of anti-infectives must urgently be developed. Antibiotics with new modes of action are needed, but other concepts are also currently being pursued. Targeting bacterial virulence as a means of blocking pathogenicity is a promising new strategy

• . Keywords: antimicrobial resistance; bacterial adhesins; bacterial toxins; pathoblockers; quorum sensing; Review 1. Antimicrobial resistance crisis for bacterial infections The current crisis caused by antimicrobial resistance [1][2] demands new strategies to fight infections. Antibiotics have served as

• life-saving drugs during the last 100 years and rescued the world from a situation where practically untreatable infections with high mortality rates were the norm. However, starting in the 1960s, the delusive belief that the available antibiotics were sufficiently effective to treat all infections led

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

• compromised individuals and in patients with bronchiectasis or cystic fibrosis. The infections become chronic, as P. aeruginosa develops resistance to conventional antibiotics due to its ability to produce virulence factors and modulate immune defenses by quorum sensing (QS) and biofilm production

• containing 5% CO2 and 21% O2. To maintain optimal culture conditions, the medium was changed twice a week. Prior the infection with P. aeruginosa and adding QSSMs the endothelial cells were cultured in a medium without antibiotics. Endothelial cells were stimulated with P. aeruginosa PAO1 strain (control

• were washed with PBS (phosphate buffered saline) and 1 mL of fresh medium without antibiotics was added to each well. Suspensions of P. aeruginosa were obtained from bacterial mid-logarithmic phase cultures grown in nutrient broth adjusted to 107 CFU/mL and 1 mL were used for the inoculation of each

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• class of antibacterial agents active also against resistant strains. Keywords: antimicrobial activity; multidrug-resistant bacteria; natural products; synthesis; tetramic acid; Introduction The treatment of bacterial infections by antibiotics is widely regarded as one of the major achievements of the

• -resistant phenotype (average MIC 32 µg/mL on 30 strains tested). Conclusion The development of novel strategies to fight bacterial infections is an imperative goal, mainly due to the increasing number of bacterial strains resistant to a wide spectrum of antibiotics. Aim of this work was the development of a

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

• significant attention as a potential antivirulence alternative to traditional antibiotics. Streptococcus pneumoniae, a notorious human pathogen responsible for a variety of acute and chronic infections, utilizes the competence regulon and its associated signaling peptide, the competence stimulating peptide

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• arylglycosylation was also extended for the synthesis of aureolic acid antibiotics [21][51][52]. In search of convenient methods for the synthesis of aryl sialosides, Gao et al. explored the scope of the Mitsunobu reaction with the sialic acid derivative 49, employing a range of phenols 50–58 in acetonitrile to

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• . Additionally, the treatment and management of viral and bacterial diseases is complicated by increasing rates of multidrug resistance. Hence, the need for new chemical scaffolds urgently required to increase the chemical diversity of drugs, especially to obtain antibiotics that overcome resistance by new modes

• other bafilomycin type antibiotics, show very little similarity in their structures. The typical α-methyl-β-hydroxy part of the bafilomycin side chain is absent in 1/2, which features a unique α-methylene group. However, both share a carbonyl function in δ-position to the macrolide, which often is

• masked as a hemiketal in bafilomycins, e.g., in bafilomycin A1 [11][12][13][14]. Bafilomycins are a family of macrolide antibiotics isolated from actinobacteria such as Micromonospora and Streptomyces species [11]. They are specific inhibitors of vacuolar ATPase (V-ATPase) [15]. The most studied compound

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

• [21][22][23][24][25], Gram-positive [26][27] and Gram-negative bacteria [28][29][30], and a marine sponge [31]. Among a variety of substituted 4-quinolones, 2-alkyl-4-quinolones are the most common core in antibiotics [32], which were originally discovered as anti-anthrax metabolites produced by

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• on surfaces [3]. They can produce a variety of secondary metabolites, including antibiotics [4][5], volatile compounds [6][7], oligohydroxybutyrates [8] and a range of N-acylhomoserine lactones (AHLs) [8][9][10]. AHLs are quorum-sensing signaling compounds that are used for cell–cell communication to

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• ' (Figure 5) [72][73][74]. In principle, the NAA-modification is inspired by 'high-carbon' nucleoside structures (i.e., nucleosides having more than five carbon atoms in the sugar unit) found in naturally occurring nucleoside antibiotics [75][76][77]. In muraymycin- and caprazamycin-type nucleoside

• antibiotics, among others, such 'high-carbon' nucleosides are uridine-derived amino acid structures ('glycyluridine', GlyU) [78][79][80], which are aminoribosylated at the 5'-hydroxy group. As part of our ongoing research program on muraymycin nucleoside antibiotics (e.g., muraymycin A1 (44)) and their

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

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• productive and biosynthetically exceptionally creative source of secondary metabolites from all classes of natural products. Many prominent compounds such as lovastatin from Aspergillus terreus [1] or the penicillin antibiotics from Penicillium [2] are used for human wellfare, whilst others including

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• antibiotics [41]. Our aim in the present study was to synthesize functionalized pyrimidinone systems through rDA reactions. Many of these products are of high importance in drug design due to their diverse biological properties including antimicrobial, antiviral, antioxidant and antitumor activities. In

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• peptides (CAMPs) and antibiotics [25][32][33][34]. Activation of the innate immune response by lipid A/LPS requires a consecutive interaction of lipid A with lipopolysaccharide-binding protein (LPB) [35], glycosylphosphatidylinositol-anchored surface protein CD14 (a differentiation antigen of monocytes

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

• modelled as a mixture of independent virtual weak bases. We already have employed these products as capping agents for the preparation of silver nanocomposites [37], which in turn have been tested as catalysts for nitroarene reduction and as antimicrobial agents in synergism with classical antibiotics [40

• maintenance by pathogenic bacteria, such as P. aeruginosa and S. aureus [60][61][62]. In addition, eDNA with its negative charge can sequester cationic antibiotics contributing to antibiotic resistance; thus, removing eDNA from the biofilm matrix can weaken the biofilm and can raise its susceptibility to

• antibiotics. The fact that these cyclodextrin derivatives might be loaded with an antibiotic allows speculating that a possible antibiotic–CD complex could target the pathogen and in the meanwhile to bind and sequester extracellular DNA, inhibiting its role in vivo. Finally, a particular mention is deserved

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

• killing by immune factors, bacteriolytic enzymes, or antibiotics. In this review, with focus on lectins relevant for drug discovery and development, the mannose-binding sites of six CLECs and three bacterial lectins are analyzed and compared with one another to answer the question: What makes for a

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• antibiotics primycin and desertomycin [10] but not in the reported cluster for mediomycin in S. blastmyceticus [8], so the enzyme hypothesised to be responsible for this step in mediomycin biosynthesis has not been identified until now. We present here the characterisation of the med biosynthetic gene cluster

• antibiotics [10]. However, careful scrutiny of the open reading frames flanking the PKS in the med biosynthetic gene cluster failed to reveal any whose product could be plausibly construed to be an amidinohydrolase. The reported S. blastmyceticus med cluster also lacks the expected amidinohydrolase [8]. We

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• applications in biology and medicine to mimic the phosphate group leading to antiretroviral drugs (e.g., tenofovir (1)) [39], isoprenoid biosynthesis inhibitors [40][41], antibiotics (e.g., fosfomycin (2)) [42], tyrosine phosphatase inhibitors 3 [43], antimalarial 4 [44], antihypertensive drugs (e.g., K4 5 and

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• as readily available starting material. Keywords: antibiotic; bromination; BSC; C–H arylation; cross-coupling; Hantzsch synthesis; thiopeptide; Introduction Thiopeptide antibiotics are a class of peptide-derived macrocycles which contain many thiazole and thiazoline units, with almost 90 structures

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• an optimized C–C cross-coupling sequence with a Suzuki cross-coupling reaction as key step. Keywords: antibiotics; polyenes; polyketides; Stille reaction; Suzuki reaction; total synthesis; Introduction The elansolids are metabolites from the gliding bacterium Chitinophaga sancti (formerly

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• aminoglycosides, well-known antibiotics [60]. Even more remarkably, when Ca(OH)2 is used in lieu of Ca(OTf)2 the 1′-β-glucoside is formed as the major product (ratio of 3′ to 1′ 30:70) in 65% total yield of the two products. To provide insight into the regioselectivity of the reaction, the authors synthesized

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• ; protein design; Review Megasynthases are proteins in natural compound synthesis Microbial natural products represent a rich source of pharmaceutically relevant chemical entities. A major class is represented by polyketides (PK) exemplified by the antibiotics erythromycin and rifamycin, by the

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

• the biosynthesis of glycosidic linkage requires the transfer of a sugar residue from a donor to an acceptor [35]. Acceptor substrates are carbohydrates, proteins, lipids, DNA, flavonol, antibiotics and steroids. In contrast, glycosyl donor substrates are mostly sugar nucleotides, such as UDP-GlcNAc

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• important to the activities of cycloheximide congeners. Keywords: antifungal activity; cycloheximide derivatives; E/Z photoisomerization; Streptomyces sp; theoretical conformational analysis; Introduction The glutarimide-containing antibiotics represent a fascinating class of natural products that exhibit