Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• start to delineate structure–activity relationships (SARs) for SdiA:AHL interactions. Using a cell-based reporter of SdiA in Salmonella enterica serovar Typhimurium, several non-natural SdiA agonists and the first set of SdiA antagonists were identified and characterized. These compounds represent new

• , and follow-up studies were performed in an E. coli SdiA reporter. The results provide a broad picture of the types of AHL scaffolds that can agonize and antagonize S. Typhimurium SdiA, allowing for the definition of key structure–activity relationships (SARs) for the modulation of SdiA activity. These

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• be more potent and selective inhibitors of the target enzyme. Moreover, proposed N-benzyl substituent at the pyrrolidine core was also confirmed to be essential for selectivity [30]. In this study, we explored structure–activity relationships (SAR) of pyrrolidine derivatives 1 with different

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

• stimulating peptide (CSP); protein–peptide interactions; quorum sensing; Streptococcus pneumoniae; structure–activity relationships (SAR); Introduction Quorum sensing (QS), a cell-density mechanism utilized by bacteria to assess their population density through the detection of diffusible signal molecules

• characterization details). Structure–activity relationships of CSP1 analogs To assess QS modulation, we utilized the β-gal reporter strains, constructed by Lau and co-worker [31]. In these strains the lacZ gene is under the control of QS (pcomX). Thus, upon QS activation, ComE will bind pcomX and transcribe lacZ

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• of selective anticancer peptide therapeutics. Keywords: breast cancer; decoralin; MCF-7 cells; peptide design; selective anticancer peptides; structure–activity relationships; Introduction Approximately 12% of U.S. women develop breast cancer according to the U.S. Breast Cancer website (http

• specific case of Dec-NH2 and its analogs, helical propensity, having higher hydrophobicity, hydrophobic momentum, and displaying a net positive charge appeared to correlate with improved antitumoral activity. These results add to our current understanding of the structure–activity relationships of ACPs and

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• enantiomeric ratio of 79:21. This method can be easily performed in large scale. In addition, the structure–activity relationships for the cinchona alkaloids catalysts were elucidated. Experimental All solvents and reagents were of commercial sources and used without further purification. Melting points were

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• [2][3]. Their high cytotoxicity prompted manifold studies that were initially focussed on the total synthesis and structure–activity relationships [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. This work resulted in the identification of cryptophycin-52, a highly biologically active

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• of cytotoxicity, structure–activity relationships and electrochemical behaviour [95]. Derivatives that contain an aromatic amine and salicylaldehyde or 2-pyridinecarboxaldehyde moieties were found to be the most active against the HL-60 (promyelocytic leukaemia) cell line. Zhou et al. obtained

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• purity. To obtain clear structure–activity relationships data on lipid A–TLR4 interaction as well as unambiguous correlation of the lipid A acylation and phosphorylation pattern to its capacity in induction of different (i.e., MyD88-dependent and TRIF-dependent) signaling pathways, numerous well-defined

• chain β-hydroxy fatty acids, anomeric phosphorylation and the synthesis of binary glycosyl phosphodiesters involving two amino sugars. Explicit structure–activity relationships data obtained with synthetic lipid A derivatives would also help to design novel therapeutic approaches for sepsis and

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

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• compounds and their precursors from Table 1 are taken into consideration, some valuable structure–activity relationships appear. 13α-Estrone (1) displays 17β-HSD1 inhibitory potential similar to that of the natural substrate estrone. Iodination at C-2 of 1 improves the inhibitory potential, resulting in a

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• analogous way. This facilitates the development of models with higher predictive performance and the identification of the factors that have the most influence over the property being modelled, leading to clearer interpretation of the structure–activity relationships represented by the model. This

G-Protein coupled receptors: answers from simulations

• Timothy Clark

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

• have often observed that in quantitative structure–activity relationships (QSAR) for GPCRs, agonists give far better results than antagonists [40]. Metadynamics simulations on the vasopressin receptor [41] revealed the reason for this behavior. As also found previously in unbiased simulations of the β2

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• [34][35], thermodynamics [36][37], structure–activity relationships [38][39] have been extensively described elsewhere, therefore they are out of the scope of this review. Herein the focus is on the various catalytic reactor systems and technological solutions reported in the literature for this

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• effectiveness of cN-II inhibitors in the treatment of these diseases [4][5]. As a result of our interest in this area, we and others [6] have investigated a number of structure–activity relationships (SAR) [7][8] and various medicinal chemistry approaches [9][10] to identify potential cN-II inhibitors. As part

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• -aryl-3-(4-methanesulfonylphenyl)pyrones 49 had been synthesized to get insights into structure activity relationships, whereby 6-methyl-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (50) showed the best combination of inhibitory concentration and selectivity (IC50 = 0.68 µM, SI = 904; Figure 11) [56

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• minutes in presence of 20b, the most toxic enantiomer, (−)-cyclosarin 14a, reacting faster in this enantioselective degradation [75]. Structure–activity relationships based on this first series of compounds revealed the determinant role of oximes’ nucleophilic strength in the hydrolysis process. Firstly

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• introduce a wide variety of substituents on 1,4-disubstituted 1,2,3-triazoles from the organic azide or terminal alkyne starting materials [1][2]. These Huisgen reactions [13] facilitate rapid drug screening by allowing for tracking in biological systems and the exploration of structure-activity

• relationships [10][14][15][16][17][18][19]. Propargylamines are a popular choice for the terminal alkyne component and form highly selective inhibitors (Figure 1) [2]. Due to the difficulty of forming tetrasubstituted propargylamines, the incorporation of deprotectable variants into triazoles is extremely rare

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• reported for different plant extracts. Model 4: DFT calculations In order to explain the structure–activity relationships of the hydroxylated biphenyls and their corresponding monomers, we have optimized the geometries of the compounds and possible phenoxyl radical species of the parent compounds. The

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• used for the construction of peptide–polymer conjugates [11][12], however, a systematic comparison of the different polymeric materials with respect to the structure–activity relationships is missing so far. The goal of this contribution is to synthesize and compare flexible multivalent ligands for an

• understanding of structure–activity relationships of polymeric ligands. For this purpose, the thermodynamics and the stoichiometry of protein binding events were determined experimentally for all multivalent ligands. Finally, atomistic molecular dynamics simulations were conducted in order to rationalize the

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

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• desirable as the incorporation of conformationally constrained α-amino acids such as 3 into peptides is frequently used to study structure–activity relationships [38][39][40]. Several methods have been developed for the preparation of analogues of β-methylphenylalanine in enantiopure form. These include

• were 37 and 45% lower than those of hormaomycin (1) itself. Further exploration of structure–activity relationships of the hormaomycins would be required to prepare new antiparasitic lead compounds. Conclusion At first sight, the oligopeptide assembly leading to hormaomycin does not appear to be a very

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• ability of this biosensor to respond to a broad range of chain lengths and functionalization makes it a good choice for the study of structure–activity relationships of synthesized analogues. The ability of the natural AHLs 3 and their halogenated analogues 6, 8 and 11 to induce fluorescence was expressed

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• allowing for an evaluation of structure–activity relationships. Results and Discussion We started our reaction sequence with an indium-mediated allylation of unprotected carbohydrates using D-arabinose (1a), D-galactose (1b) and D-glucose (1c) as starting materials. The Barbier-type chain elongation

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• nanoparticle) of the sulfated pyrans [26][27]. We were therefore interested to prepare inhibitors offering only a small number of ligands to get better information about structure–activity relationships and to study the influence of the flexible and rigid spacer units. In this report we present methods for the