Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• , enzyme inhibition, or disruption of bacterial protein synthesis. This knowledge was primarily acquired in vitro when B. subtilis was competing with other microbial monocultures. However, our understanding of the true ecological role of these small molecules is limited. In this study, we have established

• indicated that the genus Lysinibacillus was negatively affected by the addition of B. subtilis P5_B1 WT and that NRPs enhance the suppression. To dissect the direct impact of a particular NRP in this inhibition, we monitored the growth of L. fusiformis M5, a previously isolated Lysinibacillus species [54

• in the exponential growth phase. Furthermore, the effect of spent WT medium seems to be reduced at this concentration, but the spent media of ∆ppsC and ∆pksL maintained their growth inhibition potential. The lowest concentration of a spent medium having an inhibitory effect was 10.02%. At this

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• ). The inhibition by peptide 9 is found to be in a reversible and noncompetitive way. Molecular modeling shows four cationic ammonium groups forming ion pairs and hydrogen bonds with negatively charged residues, such as Glu217, Asp60B, Asp147 and Glu217, respectively and completely block the central pore

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• ), or sodium azide (known mutagen for TA 100), was also examined using the plate incorporation procedure and the results are summarized in Table 2 and Table 3. This assay proved a strong antimutagenic activity of all tested α-(arylamino)acetonitrile derivatives, with a better inhibition exhibited in the

• case of the TA98 strain (44–95%), but nevertheless considerable for TA100 strain (46–79%). The results of the antimutagenicity assay indicate a lower inhibition exhibited in the presence of liver homogenate (S9), pointing out that metabolizing enzymes could interfere with the activation of the

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• the general procedure. Biological screening The 1,4-DHP scaffold displays an extensive range of biological activities, including reversing multidrug resistance (through the inhibition of the P-glycoprotein) [26] and antiproliferative effects on human cancer cell lines [27]. We wondered whether the

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• -inflammatory [25], antibacterial [26][27], and anticancer reagents [28][29]. The latter property is mainly based on the binding interaction of berberine with nucleic acids and the resulting inhibition of topoisomerase and telomerase [2][30]. Most notably, berberine (1a) induces a strong growth inhibition in

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• described for 1 led to no detectable decomposition (Figure 3, Supporting Information File 1). Biological activity and solubility The biological activities of piperine (1) and the analog 2 were compared using two different assays, namely the inhibition of either acetylcholinesterase (AChE) or β-secretase

• (BACE-1). The inhibition of AChE was measured using a modification of a previously described colorimetric assay (Figure 4a) [33]. It quickly became apparent that the limited solubility of piperine (1) in 50 mM Tris-HCl buffer, even in the presence of methanol as a co-solvent, was a major problem in this

• assay. We observed cloudiness or the appearance of a precipitate at higher concentrations of 1, which affected the reproducibility of the assay, and prevented complete inhibition from being achieved (Figure 4a). The estimated IC50 of 1 was >1,000 μM. In contrast, analog 2 posed no solubility problems in

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• porphyrin 22 and the disulfide 12, obviously because of catalyst poisoning by sulfur [32][33]. To circumvent these problems, protection groups were introduced. Protection with methyl 3-mercaptopropionate (15) [29] was successful, however, inhibition of the Suzuki reaction was observed. We assume an alkaline

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• recent years, the focus of biochemical research and drug development has shifted from the inhibition of single enzymes to targeting protein-protein interactions [1][2], which play key roles in cellular function and dysfunction [3][4]. Enzymes usually bind their substrates in deep pockets with specific

• [8][9][10][11][12], and inhibit enzyme function [13] in vitro, they also exhibit interesting effects in vivo like the reversal of Alzheimer plaques in mice [14], tumor inhibition [15], and reduction of HIV infectivity [16], all while showing almost no toxic side effects [14][17]. In calixarenes with

• inhibition of potassium ion transport [39]. Another guanidinium-calixarene variant was designed to hold together the four tetramer subunits of a p53-R337H tumor suppressor mutant and thus restore tetramer stability [40]. Further examples for ligands targeting negatively charged patches on proteins include

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• fungus; modified Mosher’s method; Muyocopron laterale; polyketides; Introduction Azaphilones, which are a class of fungal polyketides with diverse structures, have received growing attention due to their various biological activities, such as the inhibition of some protein–protein interactions [1][2

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• an endosomal pathway. The low pKa value of the four GCP moieties could result in an improved buffering capacity, which could facilitate endosomal escape by the proton-sponge effect [28]. Significant inhibition of DNA transfection by bafilomycin (a macrolide antibiotic that can block the endosomal

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• activities [7][8]. For example, (S)-monastrol is 15-fold more effective in the inhibition of Eg 5 ATPase than its enantiomer, (R)-monastrol [9]. As more reports on the enantiospecific biological activity of DMPMs came to light, the development of an efficient and reliable asymmetric synthesis of enantiopure

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• DMSO. The respiration of live cells was quantified by the measurement of the absorption at 540 nm by a microplate reader. The experiment was run in a triplicate, and the rates of the cell-growth inhibition at each concentration were plotted on a single logarithmic chart to deduce the GI50 values of the

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• substrate of mycobacterial galactofuranosyltransferase GlfT2 in the transition state, we evaluated these compounds by computational methods, as well as in an enzyme assay for the possible inhibition of the mycobacterial galactan biosynthesis. Our data show that despite favorable docking scores to the active

• , it does have some advantages compared to the spectrophotometric GlfT2 assay [19]. Firstly, in the crude assay GlfT2 uses its natural acceptor, GL4, which could affect its activity and thus the outcome of the inhibition studies. Secondly, it allows to evaluate inhibition of the enzymes involved in GL4

• production (WecA, WbbL, UGM, GlfT1; Supporting Information File 1, Figure S1) [6] by the tested compounds, which could indicate the unspecific effects. These cannot be precluded, especially if relatively high concentrations of the studied molecules are required for achieving substantial enzyme inhibition

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• a variety of biological activities such as anticancer [24], inhibition of tyrosine phosphatase 1B, antioxidant properties, etc. [25][26][27]. Due to their numerous applications, they have found diverse uses such as thioindigo-like dyes, photoresponsive devices, and photoswitchable biomolecules [28

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• constitute a severe limitation in the employ of BER [2][3][4]. To minimize these drawbacks, its isoquinoline portion was derivatized in positions 9 and 13 that are critical for topoisomerase inhibition and quadruplex structure binding [5][6][7][8]. The insertion of a phenyl group or a benzhydryl group linked

• of tetrahydroberberine analogues with interesting biological properties. Indeed, the investigation on the antiproliferative effects highlighted the ability of some hydrazono-DHBERs and hydrazono-THBERs to induce a significant growth inhibition on the tested cancer cell line, which might deserve

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• sponge prey availability [41]. The isolated metabolites showed various biological activities, such as cytotoxicity, antimicrobial, antiviral and antitumor activities, inhibition of transactivation for the farnesoid X receptor, inhibition of mammalian phospholipase A2, and ichthyotoxicity against the

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• for peptides can be powerful tools for labeling or inhibition. Finding those binding motifs, especially in water which competes for intermolecular H-bonds, poses an enormous challenge. A dynamic combinatorial library can be a powerful method to overcome this issue. We previously reported artificial

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• the control reaction (Figure 3). Because the Fenton reaction catalyzed by Cu2+ was used to generate the hydroxy radicals, entrapment of Cu2+ by 1 was initially suspected as the mechanism of chemiluminescence inhibition. However, this speculation was ruled out by a titration experiment using Chrome

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• heterocycle is present in several alkaloids such as emetine (1) and related compounds, that exhibit biological activities such as glucosidase inhibition, anti-amoebic properties as well as activity against breast cancer cell lines [2]. Notable examples of synthetic compounds include the dipeptidyl peptidase

• IV inhibitor carmegliptin (2, DPP IV) with potential for the treatment of type-II diabetes [3][4]. A comparative study on novel classes of anticancer drugs identified benzo[a]quinolizines 3 and 4 (Figure 1) to be useful for a specific inhibition of heat shock response in cancer cells, which strongly

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• antiinflammatory activity of these compounds has been gaining attention. In our previous work, we synthesized and in vivo evaluated the bisphosphonic esters 1 and 2, finding a moderate edema inhibition upon oral and topical administration on BALB/c mice. Thus, in this work, the bioisosteric replacement of an amide

• functional group for an ester afforded the new bisphosphonates 3–6, which had a moderate oral edema inhibition (25 mg/kg dose) and a significant topical antiinflammatory activity (2 mg/ear) on BALB/c mice, with 6 being the most active hit (55.9% edema inhibition), comparable to the positive control (55.5

• % edema inhibition) on a TPA topical model. Next, to assess the acute toxicity of the synthesized derivatives, test animals were administered with 50–100 mg/kg of 3–6, respectively, by an oral route, and after 14 days, neither lethality nor a significative weight loss were observed. Finally, a structure

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• developed evogliptin (185) and it is currently approved for use in South Korea [121][122][123]. LY2497282: Eli Lilly identified LY2497282 (186) as a potent and selective DPP-4 inhibitor, also for the treatment of type II diabetes. The inhibition of GLP-1 degradation by dipeptidyl peptidase IV (DPP-4) has

• suggested, based on genetic studies, that a selective Nav1.7 inhibition, will produce robust inhibition of pain without significant side effects [134][135]. Conclusion In view of the increased significance of FAAs in the development of bioactive compounds, considerable efforts were dedicated to the

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• -free supernatant was filled into wells of agar plates, which were inoculated with the pathogenic bacteria. Subsequently, the diameters of the inhibition zones were measured after 48 h. As references, different kanamycin concentrations to generate comparable inhibition zones were used (Table S4

• , Supporting Information File 1). All analyzed wild type strains showed inhibition zones against the selected pathogens. Additionally, a comparison of the induced and the non-induced promoter-exchange mutants confirmed that the main bioactivity of all strains strongly depends on the fabclavines (Table 3

• previously [20]. Occurrence of the different fabclavine derivatives in the analyzed Xenorhabdus strains. The results are based on the MALDI–HRMS and MALDI–MS2 analyses shown in Figures S2–S29 (Supporting Information File 1). Inhibition zones of the wild type (WT) and promoter-exchange mutant strains (non-ind

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• -anisaldehyde (98), which possessed a relatively long lifetime and an energetic value sufficient for C–X bond cleavage. The participation of the triplet state 4-anisaldehyde (98) in the reaction mechanism was also confirmed by the complete inhibition of the ATRA reaction in the presence of oxygen, a triplet

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• inhibition activities comparable to that of panobinostat. Multistep syntheses afforded the visualized targets TOI1, TOI2, TOI3-rev and TOI4 whose biological evaluation confirmed the strength of HDAC8 inhibition with TOI4 displaying the greatest efficacy at varying concentrations. The results of this study

• development of novel HDAC inhibitors (HDACis) has become a rapidly evolving area where targeted inhibition has emerged in clinical research as a potential therapeutic approach for the treatment of various cancers as well as neurodegenerative disorders and immune related diseases [3][4][5]. Of specific

• classified as highly potent amongst traditional HDACis [11]. According to previous reports, panobinostat not only induces apoptosis in cells, but also stimulates cell growth inhibition, and cell-cycle arrest in a time- and dose-dependent manner. Thus, panobinostat has demonstrated high therapeutic potential

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• 22833565 with 1040 Mw) has been annotated (even though the sodium salt is the active form in vivo). Note also that while formally “P” in the heparin case is SERPINC1 (ATIII) the mechanism is an indirect one involving the activation of binding to F2 (activated thrombin) for inhibition. Another problematic

• example is mechanism-based covalent inhibition where the time dependence of IC50 for “A” is not captured. The structured capture of DARCLP by curation (or at least DARCP) has very high value from the additional relationships that can be explored via the entities and attributes as outlined below: Documents