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

• to a decline in the development of new antibiotics, with very few new antibiotics addressing a novel mode of action being brought to the market over the last four decades [3]. In parallel with the decline of new antibiotics, resistance towards these widely used drugs has evolved at a high pace and

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• known to display cytotoxic effects on diverse cancer cells by inducing a disturbance in the cell cycle and promoting apoptosis without affecting normal cellular proliferation [4][5]. In these latter cases, detailed structural criteria are still not available owing to little information about the mode of

• action of these derivatives. Amongst steroidal 17-exo-heterocycles, those containing a pyrazole heteroaromatic ring are of special relevance with respect to the above-mentioned bioactivities [6][7][8][9]. Interestingly, so far only a few examples of compounds in which a pyrazolone moiety is attached to

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• codling moth (Cydia pomonella), a major pest of pome fruits, tobacco budworm, cotton and vegetable crops [8]. Like spinosad, spinetoram elicits toxicity in the pest species via a neurotoxic mode of action. Although the exact mechanism of action has yet to be characterized, it is hypothesized that the

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• in the catalytic cycle, which itself can be classed either as reductively or oxidatively quenched. Net redox neutral processes see the substrate remain at the same oxidation state overall. These transformations are generally more complex, and the additives required as well as their mode of action

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• be amenable within the cobalt-catalyzed C–H amidation manifold by weak-coordination (Scheme 3). Given the versatility of the cobalt-catalyzed C–H nitrogenation, we became intrigued to delineating its mode of action. To this end, C–H amidations in the presence of isotopically labelled co-solvents led

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• of London dispersion in these transformations. Results and Discussion Analysis of the reaction mechanism To unravel the importance of London dispersion on the cobalt-catalyzed C–H cyanation of 2-phenylpyridine (1a), the underlying catalyst’s mode of action has to be fully understood. The available

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

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• (Dox), daunorubicin (Dau) or epirubicin are frequently used anticancer drugs. Their mode of action is based on a planar ring system which is important for intercalation into DNA [10]. In this way, anthracyclines can affect a broad range of DNA processes leading to an inhibited synthesis of

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• and pregabalin [9][10]. Later, hydrogen-bonding activation proved to be more general for obtaining Michael adducts via the addition of 1,3-dicarbonyl compounds to nitroalkenes. Chiral thioureas and squaramides, particularly those with the bifunctional mode of action, served as excellent catalysts in

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• discussion of more recent contributions. Furthermore, a detailed discussion of molecular targets and structure–activity relationships is provided. Keywords: Buruli ulcer; mode of action; mycolactones; structure–activity relationships; target elucidation; total synthesis; Review I. Mycolactones and Buruli

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

• recent years, a wealth of structural data on FAS multienzyme complexes (type I) has further deepened the insight into the principles of fatty acid (FA) synthesis [13][14][15][16][17][18][19]. Molecular mechanisms of FAS/PKS mode of action Compartmentalization Compartmentalization is a phenomenon seen

• the three iterations for product synthesis was reported (0.1 elongations per second per set of active sites) [30]. The function of ACP The molecular details underlying the ACP mode of action are currently collaboratively decoded via structural, functional and computational methods, disclosing the

• that the ACP mode of action in PKS is similar to FAS. The role of ACP in modular PKS is, however, complicated by the additional task of delivering the acyl moieties also to the downstream module (Figure 2c). Just rudimentary information on the nature of this translocation step is available; most

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• order to obtain a complete atomistic picture of the mode of action of the GPCR. A further problem is that we need structures that correspond to the receptors in their natural surroundings as they occur and function in nature. Proteins, especially membrane-bound ones, do not necessarily crystallize in

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

• findings suggested that these cycloheximide derivatives possibly exert the antifungal and cytotoxic activities via a similar mode of action. Conclusion Three new (1–3) and three known (4–6) cycloheximide congeners were obtained from the cultures of Streptomyces sp. SC0581. The structure elucidation of the

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

• afforded macrocycle 117 in 30–35% yield. Unfortunately efforts to remove both the Cbz and CO2H moieties of 117 to afford macrocycle 109 under hydrogenation conditions were unsuccessful. Conclusion The recent interest in teixobactin has resulted from its clinically unexploited mode of action, potent

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• Rollinia membranaceae by the Cortes group [100][101]. Previous studies demonstrated, that particularly adjacent bis-THF acetogenins exhibit highly potent tumor growth inhibitory activity. Detailed investigations into the mode of action revealed that acetogenins inhibit cancer cell growth through the

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• configurations at the C6’, C2” and C3” of the cis-pentacin are still undefined. Thus, the partially unresolved structure, a potent antifungal activity, the unexplored mode of action and the limited synthetic study make amipurimycin (1) an attractive target for futher investigation. As of now, a total synthesis

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

• pyocyanin inhibitors in P.aeruginosa are not directly inhibiting LasR but have an alternate mode of action(s), this hypothesis should not be completely ruled out. This may be especially relevant for compounds such as 4, which are clearly structurally distinct from OdDHL, the natural LasR agonist [12]. In

• mode of action of 4 and structure–activity relationship studies are ongoing and results will be reported in due course. BHL and OdDHL are two natural AHL-based signaling molecules used by P. aeruginosain quorum sensing. PQS is a natural quinolone signaling molecule also used by P. aeruginosa in quorum

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• bacteria was detected. The mode of action is proposed to be similar to other antifungals with a methoxyacrylate partial structure, i.e., inhibition of the mitochondrial cytochrome bc1 complex. Additionally, miuraenamide A was shown to act as actin filament stabilizer in HeLa cells [69]. The activity of

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

• natural products. These uridine-derived nucleoside-peptide antibiotics inhibit the bacterial membrane protein translocase I (MraY), a key enzyme in the intracellular part of peptidoglycan biosynthesis. This review describes the structures of naturally occurring muraymycins, their mode of action, synthetic

• biosynthesis. This review will focus on muraymycins as a subclass of nucleoside antibiotics, covering their mode of action, synthetic approaches as well as SAR studies on several derivatives. Furthermore, first insights into the biosynthesis of these Streptomyces-produced secondary metabolites will be

• address the same biological target and most likely have the same mode of action by inhibiting MraY (see below), but their in vitro activity differs significantly. It is important to notice that a comprehensive comparison of minimum inhibitory concentrations (MIC values) is difficult because naturally

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• with a minimal inhibitory concentration (MIC) of 1 µg/mL [75]. Its mode of action was deduced after genetic characterization of myxovirescin-resistant E. coli mutants [81]. The antibiotic interferes with cell-wall biosynthesis by inhibiting a novel target, i.e., the type II signal peptidase LspA, which

• prokaryotic RNA polymerase (RNAP) as mode of action for myxopyronins and corallopyronins [95][97]. Later on, mutagenesis experiments as well as binding studies indicated that the antibiotics interact with the RNAP switch region [104][105], which acts as a hinge mediating conformational changes during

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• late evening drinks. He was a natural showman and dazzled his lecture audiences with magic tricks and engaging stories. The lab worked on an array of technically challenging projects concerning natural products isolation and their mode of action. Nakanishi worked closely with several pharmaceutical

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• . In fact there are examples of N1,N2-bisarylethandiamines, which could be cyclisized to benzimidazolium salts in the presence of air, paraformaldehyde and hydrochloric acid [55], and the success of this synthetic approach was presumably crucially depending on the mode of action of O2 oxidizing the

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• raise many fundamental questions concerning the mechanisms at play. In the present paper, we report the first examples of fluorescently-labeled multivalent iminosugars designed as molecular tools to investigate the mode of action of pharmacological chaperones/correctors in cells and in vivo, and get

• properties of those multivalent dyes in aqueous media (glycine buffer at pH 10.7), are interesting, providing high quantum yields, 24% for 13a and 43% for 15a, and well-defined spectroscopic features. Altogether, these results augur well for a new class of molecular tools dedicated to rationalize the mode of

• action of pharmacological chaperones and CFTR correctors by probing uptake and mapping biodistribution in cells and in vivo. N-Bu DNJ (1) and examples of potent multivalent pharmacological chaperones and CFTR correctors (2 and 3). Azide-armed DNJ derivatives 4 and polyalkyne “clickable” scaffolds 5 and 6

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• overcome these drawbacks and to enhance the activity. In addition, their structure–activity relationships were studied to gain better insight into the mode of action. The general synthesis of curcumin itself (Scheme 1) [23][24] requires masking of the reactive methylene group of the acetylacetone moiety by

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

• biocides and modes of action As the number of biocides in use is large, some active substances as well as their mode of action are listed in Table 2 with a classification based on active chemical groups. As depicted in Table 2, the mechanism of action depends on the molecular structure of the biocides