Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• ; nematophin; Staphylococcus aureus; Introduction Microorganisms present a rich source of bioactive natural products of pharmacological importance against an emerging number of multiresistant bacteria [1]. Such examples are Xenorhabdus sp., Gram-negative entomopathogenic bacteria which live in symbiosis with

• -oxopentanoic acid and tryptamine and showed good activities against different Gram-positive pathogens like Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) comparable with activities of vancomycin. Recently, the biosynthesis of 1 was elucidated by our group as well as the 2

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• from 3-iodinated quinolones by methylation and iodine–metal exchange/oxidation. The two N- and O-methylated derivatives of the PQS showed strong quorum sensing activity comparable to that of PQS itself. Staphylococcus aureus, another pathogenic bacterium often co-occurring with P. aeruginosa especially

• . aeruginosa and Staphylococcus aureus, which model interactions relevant to patients with cystic fibrosis, HQNO is a major factor for killing of S. aureus [15]. While HQNO seems to be generally toxic to Gram-positive bacteria, we could show that some bacteria are able to transform HQNO into less toxic

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• among several other Pt(II)-based compounds to kill P. aeruginosa. It was previously reported that cisplatin had antimicrobial effects on nosocomial pathogens, such as Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus [10] and persister cells [11]. Transcriptomic analysis was employed to

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• program for their antimicrobial activity (Table 3). While the valine derivative 9 was virtually inactive, the other compounds showed some activity. Glycine compound 11 showed good activity against the Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus, and Micrococcus luteus, and against the

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• resistance: 1. Priority 1 – Critical: Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant, 3rd generation cephalosporin-resistant 2. Priority 2 – High: Enterococcus faecium, vancomycin-resistant Staphylococcus aureus, methicillin

• and Gram-negative pathogens, namely Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Acinetobacter baylyi with MICs ranging from 39 to 78 μM [62]. A year later, further SAR investigations from the same research group led to the identification of another tetrahydrocarbazole derivative 12

• peptides for their ability to disrupt PPIs in the β-sliding clamp of Staphylococcus aureus. In this elegant study, from a library of 900,000 cyclic peptides, which was intracellularly generated using the split-intein circular ligation of peptides and proteins (SICLOPPS) technology [66], three hits

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• ; quorum sensing; Staphylococcus aureus; Introduction Antimicrobial resistance is rapidly becoming a global threat [1][2]. It is estimated that worldwide, at least 700 000 people die every year from drug-resistant strains of common bacterial infections. Strategies to deal with the global antimicrobial

• system and antibiotics. The Centers for Disease Control and Prevention (CDC) have listed a number of bacteria that present serious, urgent and concerning threats [8]. One of these problematic bacteria is methicillin-resistant Staphylococcus aureus (MRSA), a human pathogen that causes a wide range of

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

• potent antibacterial activity against Helicobacter pylori and induce growth defects in Escherichia coli and Staphylococcus aureus. Taking inspiration from a methodology used in our total synthesis of natural products, we applied this methodology to access analogues possessing bulky N-substituents

• Escherichia coli reporter system [9]), an intriguing effect upon the growth of E. coli and Staphylococcus aureus was noted, which showed an extended lag phase in response to the compounds (except 4, which was inactive towards E. coli. It should be noted that in this previous publication, the graphical data

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

• ]. Phenothiazines are a privileged scaffold in drug discovery most noted for their use as antipsychotic drugs including chlorpromazine, trifluoperazine, and thioridazine. However, such drugs have also long been noted for their significant antimicrobial activity particularly against Staphylococcus aureus and

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

• factors playing crucial roles in acute virulence [55]. Staphylococcus aureus infections are characterized by the toxic action of bacterial α-hemolysin, a pore forming toxin leading to hemolysis. The antibody MEDI4893, which blocks S. aureus α-hemolysin, is currently in phase II clinical trials [56

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

• the plant Juniperus excelsa [3][4]. Leopolic acid A is endowed with antibacterial activity against Staphylococcus aureus and Staphylococcus pseudintermedius with a MIC of 16 μg/mL, and against Escherichia coli with a MIC of 128 µg/mL [3][4]. In terms of structural features, this compound contains a 4

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

• Staphylococcus aureus [11][12][13][14][15][16], Gram-positive QS systems are underrepresented in the literature. To address this issue, our research groups have been actively working to delineate the molecular mechanisms of several Gram-positive QS circuitries, including Enterococcus faecalis [17], Streptococcus

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

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

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• against the following six Gram-positive bacteria species: Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes and Streptococcus pneumoniae. The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method

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

• compound 9e (Figure 5). Antibacterial activity The antibacterial activity of compounds 4, 6 and 9 (Table 7) was studied (see Experimental part in Supporting Information File 1 for details) against reference bacterial cultures: Bacillus subtilis (strain 1211), Staphylococcus aureus (strain 2231) (Gram

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• group at 2’-OH position. To the best of our knowledge, they are the first naturally occurring aroyl nucleosides reported up to now. The biological assays showed that kipukasin A owned modest activity against Gram-positive bacteria Staphylococcus aureus (ATCC 29213) [11]. During our ongoing biological

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• against multidrug resistant Staphylococcus aureus to this family of natural products [57]. Other mutations on this enzyme generated one cembrane-type monocycle (F107A) (Scheme 2) and two non-natural fusicoccane-type diterpenes (F107Y and F149L) [57]. The latter are putative intermediates in novel routes

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• cabreuva essential oil (EO) (Myrocarpus fastigiatus) [3]. Due to its antimicrobial effects against a wide range of microorganisms such as Staphylococcus aureus, Salmonella enterica and Aspergillus niger [4], Ner can be employed as natural alternative to traditional synthetic food preservatives. To achieve

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• biological activities. Various microbes, reported in the literature, can accomplish the synthesis of pyrazinone derivatives [3][4][5][6]. For instance, phevalin (1) and tyrvalin (2), pyrazinone derivatives synthesized by a serious human pathogen, Staphylococcus aureus, act as protein kinase inhibitors

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

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• tuberculosis (Mtb) and Clostridium difficile. Remarkably, no teixobactin-resistant mutants of Staphylococcus aureus or M. tuberculosis could be detected after sub-lethal dosing of the compound over a 27 day period [43]. This lack of resistance development may possibly be attributable to the mechanism of action

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• ) as a positive control. Compounds 2, 5, and 6 showed moderate α-glucosidase inhibitory activity with IC50 of 87.8, 52.3, and 95.6 μM, respectively. The other compounds were inactive (> 300 μM). Compounds 1–9 were also evaluated for antibacterial activities against Staphylococcus aureus, Staphylococcus

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• residue, which in turn, is connected to the ureido dipeptide L-Phe-L-Val. The compound showed antifungal and antibacterial activity against Mucor hiemalis and Staphylococcus aureus with a MIC of 32 and 16 μg/mL, respectively [2]. Compounds containing the isomeric 2,4-pyrrolidinedione ring system (tetramic

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• of RiPPs cyclised by serine protease-like enzymes. C) Examples of RiPPs cyclised by cysteine protease-like enzymes. Structure of autoinducing peptide AIP-I from Staphylococcus aureus and the sequence of the corresponding precursor peptide AgrD. Radical cyclisation in RiPP biosynthesis. A) AlbA