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

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• of the superoxide ion leading to the synthesis of tetrachloroaryl/vinyl-substituted nortricyclenes through its dual mode of action has been reported. KO2 was found to be superior and the only reagent to perform this kind of reaction over other conventional bases. Addition of the antioxidant BHT (2,6

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• analysis of proteins is the activity-based protein profiling (ABPP) [11][12]. This proteomic strategy uses small probes designed to target active members of enzyme families [13]. These are often based on natural products to investigate their protein targets and eventually their mode of action [14][15

• terminus without loss of function [35]. Thus the alkyne modified α,β,γ,δ-unsaturated aldehyde 10 can serve as a tool for the elucidation of the mode of action of the compound class of polyunsaturated aldehydes. DDY (10) was initially transformed with L-lysine to form an imine before CuAAC was performed

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• and the existence of a greater amount of these anions (100%) than the phosphate anions (38%) at pH 7.0 in 1.0 M solutions [21][30]. Thus, phosphate and sulfate anions show some differences in their mode of action which was evident from the rate of formation of CDRF and LC in their presence. This was

Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• . inhibens or other TDA-producing bacteria from the Roseobacter clade as promising candidates to be used as probiotics in aquacultures [12]. The mode of action of TDA is unknown, but it is difficult to select resistant and tolerant strains from long-term exposures to sub inhibitory concentrations of TDA

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• derivatives and acrylate esters 44) in the presence of Pt((R,R)-Me-DuPhos) complexes (Scheme 14). However, the products 45 suffered from low enantioselectivities [121]. The mode of action is based on the activation of the P-nucleophile. The proposed mechanism includes the P–H oxidative addition to platinum

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• the photoreactive derivative proved to be less active by a factor of at least 200. COMPARE analysis indicated tubulin interaction as likely mode of action of malevamide D. Keywords: cytotoxicity; diazirines; dolastatin analogs; marine natural products; peptides; total synthesis; Introduction The

• subnanomolar range (IC50 values about 0.7 nM). Closely related to malevamide D (1) is isodolastatin H (2), which is also active in vivo, but slightly weaker than dolastatin 10 (3) [2]. Although there has been no study regarding the mode of action, it can be assumed that malevamide D (1) acts similarly to

• ), and PXF-1118 (pleuramesothelioma, IC70 > 100 nM, IC50 about 50 nM, each). Diazirinyl-substituted malevamide D 30 was about 200 times less cytotoxic than 1. To obtain clues on the likely mode of action of 1 and 30, the in vitro activity data were compared with those of 177 reference compounds by

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• ], antimalaria and anticancer [10][11][22][23][24][25] as well as diverse further bioactivities. Recently it was discovered that prieurianin (2) impairs the actin cytoskeleton by a mechanism that does not involve direct interaction with actin suggesting that its mode of action differs from previously known

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• . Gaich et al. [38][39] used the DVCPR in a biosynthetic investigation targeting the dimethylallyltryptophan synthase. In order to test the biosynthetic hypothesis of the mode of action of the 4-prenylation of indoles by Arigoni and Wenkert (starting from L-tryptophan and dimethylallyl pyrophosphate

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• carcinoma cell line Colo 320. Due to the lack of a larger portfolio of survivin antagonists, SF002-96-1 may serve as lead structure for the development of novel cancer therapeutics. Further investigations on the cellular targets and the mode of action of the compound are now under way. Experimental General

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• farming industry and also has potent killing activity against insects, nematodes and fungi. The mode of action of antimycins is to inhibit cytochrome c reductase in the electron transport chain and halt respiration. However, more recently, antimycin A has attracted attention as a potent and selective

• inhibitor of the mitochondrial anti-apoptotic proteins Bcl-2 and Bcl-xL. Remarkably, this inhibition is independent of the main mode of action of antimycins such that an artificial derivative named 2-methoxyantimycin A inhibits Bcl-xL but does not inhibit respiration. The Bcl-2/Bcl-xL family of proteins are

• -formamidosalicylic acid moiety and they comprise more than 40 known members (Figure 1) [15][16][17][18][19][20][21][22]. Antimycins can undergo base-catalysed decomposition resulting in the production of volatile blastmycinones and butenolides [23]. The main mode of action of antimycins is to inhibit cytochrome c