Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice

• useful for understanding the action mechanism of related drugs, as well as to drive the synthesis of new drug like compounds. Since the milestone work by Hansch and Fujita [1], a variety of MD´s have been developed to improve the correlation of chemical structures with bioactivity, ranging from

• ], but these are mostly complementary and are aimed at corroborating and/or rationalizing the results provided by the regression models, since the docking methodology itself provides intermolecular energies and docking scores that correlate with bioactivity. On the other hand, despite not encoding

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• see Table 2 and Table 3. Bioactivity tests Evaluation of antileishmanial activity L. donovani (strain LG13, MHOM/ET/0000/HUSSEN), L. infantum (MHOM/GR/2002/GH12) and L. amazonensis (MPRO/BR/72/M1845) promastigotes and the murine macrophage J774 cell line (American Type Culture Collection, Manassas, VA

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

• complement the bioactivity of myxovirescins and, thereby, expand the prey spectrum. Alternatively, it is possible that the killing of M. luteus involves a different predation strategy (e.g., attack with hydrolytic enzymes). In any case, the coordinate production of antibiotics, such as myxovirescin A

• -positive bacteria. Bioactivity-guided fractionation then led to the identification of the gulmirecins as the active principles [87]. Chemically, the gulmirecins form a novel class of antibiotics together with the disciformycins [92], which were discovered in a different P. fallax strain upon a large-scale

• bioactivity data of the disciformycins suggests that the isovalerate motive is important for the antibacterial activity. Due to their potent effects against human pathogenic staphylococci as well as negligible toxicity, gulmirecins A and disciformycin B have become promising candidate compounds for the design

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• involved in inflammation reactions. The authors isolated 23, 24 and 27 from the feces of Trogopterus xanthipes (flying squirrel) by bioactivity-guided fractionation, and determined IC50 values for the pure compounds to be in the low mM range (1.33, 1.07 and 2.33 mM, respectively) [31]. Also estrogenic and

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs. Keywords: binding energy; bioactivity; cyclodextrins; hesperetin; naringenin; Introduction Flavonoids are secondary metabolites

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• compound. In conclusion, these feeding experiments using isotopically labeled precursors supported the biosynthetic assembly from an unusual PKS starter unit which results in the remarkable scaffold for the bioactivity-generating functionalities. A similar study showing the enduring significance of labeled

• -ribosomal peptides Non-ribosomal peptides often exhibit a high bioactivity and are biosynthesized by non-ribosomal peptide synthethases (NRPS) [33], which work RNA-independent and catalyze the assembly of both proteinogenic and non-proteinogenic amino acids in a modular fashion. Moreover, NRPSs can contain

• products and are remarkably diverse in structure, bioactivity, and use. Prominent examples such as the antimalaria drug artemisinin (28) from Artemisia annua, ingenol (29) and its derivatives from Euphorbia ingens [56], or the anticancer drug paclitaxel (30) feature highly functionalized polycyclic carbon

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• key intermediate to make the subsequent amide formation feasible (Scheme 1b). In our work, azoles have been chosen as the amines due to their special bioactivity [31]. To the best of our knowledge, Cu salt has not yet been used for catalyzed, oxidative direct amide formation. We report the first

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• analysis of indiacen B (2, ORTEP drawing with ellipsoides at 50% probability). Supporting Information Supporting Information File 244: Experimental procedures, bioactivity tables, X-ray figures and tables, HPLC chromatograms and NMR spectra for all compounds, NOESY analyses. Acknowledgements We thank

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• are also discussed. Pyridoacridines were found to have a large spectrum of bioactivity and this review highlights and compares the pharmacophores that are responsible for the observed bioactivity. Keywords: biosynthesis; 13C NMR shifts; pharmacophores; pyridoacridines; synthesis; Introduction In

• , terpenoids, phenolics, polysaccharides and alkaloids [4]. Various bioactivity functions such as anticancer [5][6][7], phytotoxicity [8][9][10][11], antioxidant [12][13][14][15][16], antimicrobial [17][18][19], analgesic [20][21], hypotensive [22], hypoglycemic [23], antiprotozoal [24] and plant protecting

• ] that summarize their bioactivity. Herein, a synopsis of the newly published bioactivity of pyridoacridine will be provided as well as pharmacophores associated with the activity and a discussion on the evolution of the bioactivity and the structure modification. Cytotoxicity The biologically tested

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• and nanomaterials is a challenging task. Huang and co-workers [165] have reported a taco complex template method to synthesize a cryptand/paraquat [2]rotaxane and [2]catenane (e.g., 207) by using RCM as a key step. Structural features and interesting bioactivity of the hirsutellones have grabbed the

New depsidones and isoindolinones from the mangrove endophytic fungus Meyerozyma guilliermondii (HZ-Y₂) isolated from the South China Sea

• Senhua Chen,
• Zhaoming Liu,
• Yayue Liu,
• Yongjun Lu,
• Lei He and
• Zhigang She

Beilstein J. Org. Chem. 2015, 11, 1187–1193, doi:10.3762/bjoc.11.133

• of bioactivities including antibacterial [10], antifungal [6], antiviral [12], antioxidant [5], and cytotoxic [9]. In the last decade, our research group has been focused on isolating novel compounds from endophytic fungi growing on mangroves in the South China Sea and investigating their bioactivity

• ). In the bioactivity assay, all depsidones showed strong α-glucosidase inhibitory activity with IC50 values ranging from 2.1 to 13.3 μM. Details of the isolation, structure elucidation, and biological activity of these compounds are reported herein. Results and Discussion Botryorhodine E (1) was

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• synthesis of pharmaceutically relevant building blocks has always been a significant goal in organic synthesis. Moreover, modification of natural products is also an important approach to identify promising anticancer agents. Especially due to the bioactivity of lukianols, many groups accomplished the

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• higher bioactivity compared to their corresponding homodimers [57]. BMP receptors (BMPRs) belong to the group of serine/threonine kinase transmembrane receptors and are subdivided into type I and II receptors [64][65]. There are three type I receptors, namely BMPR-IA (also known as ALK-3, activin

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• hepatitis and depression, and as topical antimicrobials for wounds and snake bites [2][3][4][5]. There is great interest in secondary metabolites produced by plants from the Hypericum genus due to the bioactivity of many compounds that have been isolated from this source. A wide variety of compounds have

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

• bioactivity of the natural compounds are typically limited. Thus far, no example of very strong anti-angiogenic activity in the nanomolar range has been found. Thus, synthetic approaches for the production, diversification and optimization are required. The modification of the polyphenol structures to improve

• their stability and bioactivity and further enhance their anti-angiogenic activity is the main goal of current research in the field. Analogs of the natural phenols with improved drug properties may be promising candidates for future oncology treatment. Structure of 4-hydroxybenzyl alcohol (HBA, 1

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• of the obtained spectra revealed that the non-symmetric dimers 9, 10 and 11 are formed preferentially. The abundance differences observed are mostly lower than 2-fold, in one case up to ca. 4-fold. This is still acceptable for our initial bioactivity assays, as most screening setups cover several

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• important target in the inflammation response (Scheme 18). The α-methoxy group introduced could then be intercepted via an N-acyliminium ion intermediate with a variety of C–C bond forming reagents. The compounds prepared were interrogated for bioactivity against α-L-fucosidase and related targets and IC50

• synthesis of the natural product, nazlinine 117. Nazlinine was isolated in 1991 from the plant, Nitraria schoberi, and exhibits serotonergic bioactivity. There had been only two previous syntheses of nazlinine and neither was sufficiently modular to prepare not only nazlinine but structurally similar

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• bioactivity-guided fractionation, the bioactive compound chelerythrine (21, a quaternary benzo[c]phenanthridine alkaloid) was isolated from Chelidonium majus L. [103]. In addition to strong antihelmintic activity (against D. intermedius), chelerythrine also showed antimicrobial, antifungal and anti

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

• ], chlorhexidine [27] and iodine [28]. In the case of pesticides, their impact on the environment is not harmless (e.g., some herbicides have an influence on bees) [29]. To improve their bioactivity as well as their stability on storage, their physicochemical characteristics, biocides can be easily encapsulated by

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

• influence of a halogen introduction, the bioactivity of these novel N-α-haloacylated homoserine lactones was directly compared with a broad library of naturally occurring AHLs. Results and Discussion Synthesis of N-acylated homoserine lactones and halogenated analogues (S)-Homoserine lactone hydrobromide (1

• activity and the absence of antagonistic effects presently demonstrated. Conclusion In conclusion, new AHL analogues were designed by introduction of a halogen atom in α-position of the N-acyl chain and their bioactivity as QS modulators has been evaluated. α-Halogenated AHL analogues exhibited a reduction

Effect of cyclodextrin complexation on phenylpropanoids’ solubility and antioxidant activity

• Miriana Kfoury,
• David Landy,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2014, 10, 2322–2331, doi:10.3762/bjoc.10.241

• limited water solubility, stability and poor bioavailability [8][9]. Thus, their encapsulation may enhance their apparent solubility without losing their structural integrity and bioactivity. During the past years, cyclodextrins (CDs) have been widely used as encapsulating agents to enhance the solubility

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• applications are also supported by the preliminary bioactivity screening of the AP-series, which revealed low cytotoxicity toward human cell lines. Experimental General 7,16-Bis[2-(3-bromopropoxy)benzoyl]-5,14-dihydrodibenzo[b,i][1,4,8,11]tetraazacyclotetradecine, 7,16-Bis[2-hydroxybenzoyl]-5,14-dihydrodibenzo

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• bioactivity. The desirable properties of any new PPG candidate are 1) absorption at wavelengths near or above 400 nm, 2) enhanced chemical and photochemical quantum yields and 3) improved rate of release, ideally in the range of ps to ns time constants; all three are useful properties for applications in

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• bioactivity of these lectins in host recognition and adhesion in biofilm formation represents an attractive antibacterial strategy, as multivalent carbohydrate motifs on cell surfaces are known to mediate a broad range of cellular and tissue adhesion processes. Carbohydrate recognition in biological systems

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• various types of bioactivity, e.g., herbicidal [12], inhibition of cell growth and enzyme activity [13][14][15][16][17][18], inhibition of voltage-gated sodium channels [19] and metabotropic glutamate receptor-5a (hmGluR5a) [20]. Consequently, our second aim was to extend the reaction to the preparation