Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• , diethylcarbamazine, ivermectin and praziquantel are insufficiently efficacious, contraindicated in some populations, or at risk of the development of resistance, thereby impeding progress towards World Health Organization goals to control or eliminate these neglected tropical diseases. However, there has been

• cattle treated annually is hundreds of millions [1]. Treatment of horses, other equids, and companion animals is also a major use of anthelmintics. Anthelmintic drug discovery has been a continued emphasis in the animal health industry, driven by the spread of resistance to the macrocyclic lactones [2

• ]. In the past 25 years, three new classes of anthelmintic drugs have reached the market: derquantel, emodepside and monepantel. However, the continuing emergence of anthelmintic resistance combined with less predictable infection patterns due to changes in climate have resulted in a breakdown of

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• 10 mm diameter each LED. The LEDs were serially connected in blocks of 6, with the minimum voltage possible (3 V) and a resistance of 60 Ω (according to Ohm's law). The output power per LED unit (blue, 465 nm) was 250 kmcd; the optical output power of the PCB of LEDs measured with a photometer

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• thicker layers of Cu on Au nanoparticles. Other findings in this study were: a) copper leaching decreased using gold nanoparticles, b) increasing the dendron generation increased the diffusion resistance. As shown in Scheme 5, a silica nanomaterial was decorated with a novel copper complex of poly(N

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• , HPPD inhibiting herbicides are advantageous because of their low toxicities, high efficiencies, broad-spectrum weed control, and safety toward crops and the environment [13][14][15]. However, the abuse of HPPD inhibitors has led to increased weed resistance and crop damage. Furthermore, the long-term

• applications of a single herbicide result in the resistance of the weed to the agent [14]. Therefore, exploring effective HPPD-inhibiting compounds for the control of resistant weeds is an emergent and important objective [2]. A considerable number of HPPD inhibiting herbicides have recently been

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• hemithioindigo-based indanone-like tubulin inhibitors (HITubs) and optimised their cellular potency as antimitotic photopharmaceuticals. These HITubs feature reliable and robust visible-light photoswitching and high fatigue resistance. The use of the hemithioindigo scaffold also permitted us to employ a para

• photoswitching (λ = 450 nm for Z → E and 530 nm for E → Z switching), with the high fatigue resistance characteristic of HTIs. The E-isomer's thermal half-life in EtOAc or DMSO was ca. 40 s (Figure 3 and Supporting Information File 1, Figure S3). Its absorption spectra and photoswitchability were unaltered by

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-ʟ-arabinose, would thus restore the activity of cationic antimicrobial peptides and several

• derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety. Keywords: antibiotic resistance; glycosyl phosphonate; glycosyl transferase; lipid A

• important, e.g., when connected to dolichol in mammalian systems or to undecaprenol in prokaryotic donor substrates for bacterial glycosyltransferases [2]. 4-Amino-4-deoxy-ʟ-arabinose (Ara4N) is an important microbial carbohydrate in bacterial lipopolysaccharides (LPS) and has been implicated in resistance

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• ; mutasynthesis; NRPS; peptide synthesis; Introduction Resistance to antibiotics is currently a major threat to public health. Especially Gram-negative bacterial pathogens are of concern, due to their widespread development of resistance mechanisms. To address this general antimicrobial resistance problem, new

• , encoded by the gene fusA1) as their target [11][12]. The co-crystal structure of argyrin B (2) and P. aeruginosa EF-G1 provides structural information of the complex at atomic resolution as basis for further structure-based optimization [11]. Jones and colleagues analyzed possible resistance mechanisms to

• argyrin and established argyrin B as an efflux substrate. Further, they showed that in susceptible Stenotrophomonas maltophilia, resistance appeared by mutational inactivation of the gene fusA1 and overexpression of the alternative elongation factor FusA2 [13]. Due to the dual activity spectrum

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• ]. The isozymes of NPPs are involved in the pathophysiology of different diseases, such as calcification, cancer, and insulin resistance [34][35]. All derivatives of compounds 5 were tested for human recombinant NPPs, i.e., NPP1–3. In addition, we compared the obtained results with those of recently

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• membrane potential (Rp) = 29.3 ± 3.9 mV and 28.3 ± 7.6 mV; holding currents at −40 mV were 77.65 ± 30.0 pA, and 76.96 ± 38.9 pA; and the input resistance (RInput) = 215.2 ± 36.1 MΩ and 209.1 ± 40.7 MΩ (mutant vs WT, n = 5 cells each). These data show treatment with 1 does not change the electrical activity

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• ) direction over an 800 mV window roughly centered on the reduction of Fc/Fc+ redox couple at a scan rate of 0.1–0.5 V/s, 10−4 A sensitivity, and 1 mV sample interval. Internal resistance (iR) compensation was manually set to 95–99.5% of the measured resistance so that the peak separation for the reversible

Ultrafast processes triggered by one- and two-photon excitation of a photochromic and luminescent hydrazone

• Alessandro Iagatti,
• Baihao Shao,
• Alberto Credi,
• Barbara Ventura,
• Ivan Aprahamian and
• Mariangela Di Donato

Beilstein J. Org. Chem. 2019, 15, 2438–2446, doi:10.3762/bjoc.15.236

• a widespread use of the most commonly employed systems have indeed often be related to low quantum yields or poor photochemical stability, low fatigue resistance, or difficult synthesis. Furthermore, in the specific case of biological applications, inappropriate absorption wavelength is often an

• -photon excitation (i.e., near infrared (NIR) light), which is also maintained in serum and solid state, has a very high photochemical stability and excellent fatigue resistance. Although the main photochemical properties of this molecule have been recently reported [29], a detailed analysis of its

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• irradiation (313 nm, toluene, c = 3.4 × 10−5 M). Inset: fatigue resistance upon multiple subsequent irradiation with UV (365 nm) and visible light (green LED) in acetonitrile. Molecular structure of complexes 8 (top) and 9 (bottom) at 100 K. The H atoms are omitted for clarity; the thermal ellipsoids are

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• ring-opening process from the ring-closed photoisomer to the original ring-opened photoisomer. The photo fatigue resistance of Glyco-DTE was then examined at 550 nm via an alternate irradiation with UV and visible light at room temperature. The ring-closing/opening cycles of Glyco-DTE could be repeated

• emission fatigue resistance was also examined and found to tolerate more than five switching cycles in PBS buffer (Figure 1D). Similar performances were also observed for control reporter 8o (Supporting Information File 1, Figure S1). The characteristic photoswitchable ON/OFF fluorescence signals as well

• as the robust fatigue resistance suggest the reporter designed here has great potential for photoswitchable fluorescence imaging in biological systems. Fabrication of Glyco-DTE@MnO2 glycosheets The fast and simple synthesis of 2D MnO2 nanosheets was performed according to reported procedures [31][32

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• (470 nm, 530 nm). The on-switching of fluorescence due to the ring-closure reaction was observed also with visible light of 470 nm (to an extent of 10% for compound SyOTh1) and attributed to the Urbach tail effect. Due to a high degree of fluorescence modulation (>270), good fatigue resistance and

• fatigue resistance. In acetonitrile solution, extrapolation of the first 160 switching cycles predicted that >3500 switching cycles may be expected before a 50% signal loss will occur. The high fatigue resistance of compound SyTh1 indicated that nonoxidized DAEs may, in general, be more photostable than

• resistance and large fluorescence quantum yield, compound SyOTh1 may be an excellent marker for single-molecule based super-resolution fluorescence microscopy, e.g., MINFLUX and STORM. In addition, SyOTh1 presents a remarkable on-switching of 10% of its maximal fluorescence signal with 470 nm light, and the

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• -stimulating, and anticancer activities [2]. Since the World Health Organization (WHO) declared antibiotic resistance a global threat and urged the search for new antibiotics, the interest in fungal metabolites increased recently. In order to find new structural types, novel source organisms have to be

• laboratory [4]. E. terrae produced a novel antibiotic called teixobactin with no detectable resistance, as it interacts with key functions of cell wall synthesis that do not undergo fast evolutionary changes [5]. Inspired by this approach we developed the Fungal one-step IsolatioN Device (FIND), in order to

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• , 50 µM in 5% DMSO (v/v), in assay buffer at the thermal equilibrium and the photostationary states (PSS) after 365 nm or 452 nm radiation. (Right) Fatigue resistance of 11, 50 µM in 5% DMSO (v/v), in assay buffer over 10 cycles of alternating 365 nm and 452 nm radiation. Reagents and conditions: a

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• 630090, Russian Federation Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, Institutskaya 3, Novosibirsk 630090, Russian Federation 10.3762/bjoc.15.200 Abstract Sterically shielded nitroxides of the pyrrolidine series have shown the highest resistance to reduction. Here we report the

• ; sterically shielded nitroxide; Introduction Sterically shielded nitroxides are currently attracting much attention due to their high resistance to bioreduction [1][2]. It has been demonstrated that 2,2,5,5-tetraethylpyrrolidine nitroxides have the highest stability, sometimes exceeding that of trityl

• -enylmagnesium bromide to the corresponding nitrone, oxidation to alkenylnitrone, intramolecular 1,3-dipolar cycloaddition, and isoxazolidine ring opening. Nitroxide 1 showed both an unexpectedly low reduction rate [6] and long relaxation times t1 and tm at room temperature [4]. Unexpectedly high resistance of

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• jars manufactured from thermoplastic materials as alternatives to Teflon, having high mechanical resistance, rigidity, and hardness, we were pleased to find that Ertalyte® displayed an excellent performance in the mechanical process. All other parameters being equal, the conversion efficiency improved

• abrasion-, chemical and moderate acid resistance, with a low coefficient of friction and FDA approved [69]. In the absence of TEMPO, the oxidation reaction did not work anymore, while in the absence of KBr, the conversion rate was considerably reduced. The use of bases other than NaHCO3 (Na2CO3 or sodium

Synthesis of 9-O-arylated berberines via copper-catalyzed C_Ar–O coupling reactions

• Qiaoqiao Teng,
• Xinhui Zhu,
• Qianqian Guo,
• Weihua Jiang,
• Jiang Liu and
• Qi Meng

Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161

• elaborate motifs such as heterocycles [10][11][12], glucose [13], nitric oxide [14], and the multidrug-resistance pump inhibitor 5-nitro-2-phenylindole (INF55) [15] have been covalently attached to BBR, further widening its pharmacological spectrum. Aromatic rings are another family of substituents having

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• Leticia Monjas Peter Fodran Johanna Kollback Carlo Cassani Thomas Olsson Maja Genheden D. G. Joakim Larsson Carl-Johan Wallentin Department of Chemistry and Molecular Biology, University of Gothenburg, Kemigården 4, 412 96, Gothenburg, Sweden Centre for Antibiotic Resistance Research (CARe

• : abyssomicin C; antibiotic; antibiotic resistance; MRSA; truncated natural products; Introduction Antibiotic resistance is a major threat to global health, and numerous actions are presently taken in both academia and industry to combat this major societal challenge. There are many different approaches to

• Supporting Information File 102: Experimental part (modelling and docking, synthesis and biological evaluation), and copies of NMR spectra. Acknowledgements The Olle Engkvist Byggmästare foundation, the Centre for Antibiotic Resistance Research at the University of Gothenburg (CARe) and the Swedish Research

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• experiments; a very hazy solution was obtained, which was inseparable by centrifugation, after dialysis. Filtration through a 0.22 µm hydrophilic membrane showed poor resistance, meaning that particle sizes were low and dominantly <0.2 µm. Experiments to clarify the situation and determine the composition of

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• 125 mg/L. A bacteriostatic activity against S. aureus was observed only at the higher concentrations of 250 and 500 mg/L. The same situation was found for the tested E. coli strain. The gram-negative bacterium P. aeruginosa showed resistance to all compounds tested in the given concentration range

N-doped carbon dots covalently functionalized with pillar[5]arenes for Fe³⁺ sensing

• Jia Gao,
• Ming-Xue Wu,
• Dihua Dai,
• Zhi Cai,
• Yue Wang,
• Wenhui Fang,
• Yan Wang and
• Ying-Wei Yang

Beilstein J. Org. Chem. 2019, 15, 1262–1267, doi:10.3762/bjoc.15.123

• stability, and high resistance to photobleaching. Thus, fluorescent C-dots have been widely applied in the fields of imaging, catalysis, and sensing [5][6][7]. With the rapid development of fluorescent C-dots, much effort has been made to tune their electrical, optical, and chemical properties via doping

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• complex BHQ template. Furthermore, using a BHQ template could be a valuable alternative to TG-based compounds, should the latter encounter problems such as low bioavailability or drug resistance. The first step towards the development of BHQ-based compounds of therapeutic value is the establishment of a