Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• pyrazolidinone derivatives like LY186826 and its analogues with antibacterial activity [8][9][10][11][12]. The chemistry of azomethine imines has been actively investigated since the second half of the last century but their reactivity is still far less studied compared with nitrones or azomethine ylides – other

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

• configurations were determined using the modified Mosher’s method and through comparisons of experimental and calculated electronic circular dichroism data. In addition, muyocopronone B (2) was found to exhibit a weak antibacterial activity against some Gram-positive bacteria. Keywords: azaphilones; endophytic

• ,10R,11R) stereoisomer. Finally, since a number of azaphilones have been reported to exhibit antimicrobial activity [5][23], muyocopronones A (1) and B (2) were screened for their antibacterial activity against five strains of Gram-positive bacteria, namely Staphylococcus aureus (PAGU 273T

• ), methicillin-resistant S. aureus (PAGU 841, MRSA), S. epidermidis (PAGU 283T), Enterococcus faecalis (PAGU 102T), and vancomycin-resistant E. faecalis (PAGU 100). Although muyocopronone B (2) exhibited an antibacterial activity against both antibiotic-resistant and antibiotic-susceptible strains, with minimum

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

• . Antibacterial assay The antibacterial activity was evaluated by a microculture technique described previously [20], except for a 1:100 reduction of the seeding density of T. maritimum NBRC16015. Cytotoxicity assay 3Y1 rat embryonic fibroblastic cells were maintained in low-glucose DMEM medium containing ʟ

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

• the genus Doriprismatica and scalarane-containing dictyoceratid sponges of the Spongiidae family. The results also indicate that D. stellata passes the scalarane metabolite on to its egg ribbons, most likely for protective purposes. The scalarane showed antibacterial activity against the Gram-positive

• sesterterpene reported with a cyclopropane ring bridging the carbons C-3, C-22 and C-4 in ring A, and an acetoxy group at C-11 instead of C-12 in ring C (Figure 2). All ethyl acetate extracts, as well as the isolated new scalarane, showed antibacterial activity against the Gram-positive bacteria Arthrobacter

• and Spongia cf. agaricina (Figure 3). It was isolated from both samples (egg ribbons: 1 mg, 0.1% wet weight; sponge: 0.7 mg, 0.02% wet weight) and the identity was validated by comparison of the MS and NMR spectra. Antibacterial activity All ethyl acetate extracts from Doriprismatica stellata

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• assignment of an E geometry at C8 in 2. As metabolites of microbes, compounds 1 and 2 are unprecedented in terms of bearing a 2,4-dienone system. Both 1 and 2 showed antibacterial activity against the plant pathogen Rhizobium radiobacter and the fish pathogen Tenacibaculum maritimum, with a contrasting

• and 2 showed selective antibacterial activity against the plant pathogen R. radiobacter and the fish pathogen T. maritimum, respectively. In addition, both 1 and 2 displayed agonistic activity against PPARα and PPARγ. Experimental General experimental procedure UV and IR spectra were recorded on a

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• , we noticed that there was generally a poor correlation between the antibacterial activity on the one side, and the cytotoxicity against HeLa cells on the other side, and erythrocytes as a third scenario. Different compounds could thus be regarded as potential leads for chemotherapy of either

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• of NMR and MS spectroscopic data. The NMR assignment of 1 was assisted by DFT-based theoretical chemical shift calculation. Compound 2 showed antibacterial activity against multidrug resistant Salmonella enterica ser. Typhi with a MIC of 125 µg/mL while 1 was not active. Keywords: aromatic

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• ’-methoxy group to halogens or other substituents in different positions led to a loss of antibacterial activity, whereas the 5’-methoxytryptophan regioisomer largely retained activity against P. aeruginosa PAO1. Inspection of the crystal structure of argyrin in complex with the bacterial elongation factor

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• cell lines, two bacteria, one fungus and one plant (Table 4). Compound 1 was inactive up to 100 μg mL−1 in all of the assays performed, suggesting acylation at 6-OH is important for biological activity. Compounds 4, 5 and 7 showed moderate antibacterial activity against B. subtilis, with weaker

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• wavenumber values for the lactone C=O stretch was also observed for bands assigned to the C=C bonds as consequence of their conjugation. Evaluation of the growth inhibition and hemolytic activity of S. aureus for the solonamide analogues Initially, the antibacterial activity of all analogues 9 was tested by

• range of 300–0.3 µM. None of the compounds presented antibacterial activity against S. aureus, since no MIC value could be obtained in the range of concentrations tested (MIC > 300 µM). Subsequently, a screening assay was carried out to evaluate the effect of these compounds on the hemolysis of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• presence of acetic anhydride produced a crude acetamido ester (R)-132 which was transformed into the final N-benzyl amide (R)-130 with of 99.9% ee after crystallization. ʟ-(+)-Furanomycin (Scheme 35) is a natural nonproteinogenic amino acid which showed pronounced antibacterial activity. From several

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• number of drugs and [1,2,4]triazolo[4,3-a]pyridines were shown to have herbicidal [5][6], antifungal [7], neuroprotective [8][9] and antibacterial activity [10]. In addition, [1,2,4]triazolopyridine has been used as electron-acceptor unit in the synthesis of organic light emitting diodes (OLED) [11]. 2

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• , Gothenburg, Sweden 10.3762/bjoc.15.147 Abstract The synthesis and antibacterial activity of two new highly truncated derivatives of the natural product abyssomicin C are reported. This work outlines the limits of structural truncation of the natural product and consequently provides insights for further

• physicochemical properties that NPs typically show [3]. Abyssomicin C (AbC) is an NP with antibacterial activity that was isolated from the marine actinomycete strain Verrucosispora AB-18-032 in 2004 [4][5]. It shows antibacterial activity against Gram-positive bacteria, including resistant pathogens such as

• the same time, and these compounds did not show any antibacterial activity (Figure 1). Consequently, the enone moiety of AbC was proposed to play an essential role in the antibiotic activity. Indeed, in a subsequent study it was shown that AbC has a unique mechanism of action amongst NPs: it is a

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• ) and antibacterial activity (center and right). ORTEP plot of 5-benzoyl-3-phenyl-1H-pyrazole (6a) (thermal ellipsoids at 30% probability); the direction of intermolecular N−H···O hydrogen bonding is indicated by dashed lines. Ellipsoid plot of 1-Boc-5-benzoyl-5-hydroxypyrazoline 5a. ORTEP plot and

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity. Keywords: antibacterial activity; Doebner reaction; pyrazolo[3,4-b]pyridine carboxylic acids; Ugi reaction; Introduction Modern medicinal

• experiments. Particularly, the evaluation of the antibacterial activity of the small library of new compounds 11 and 12 was carried out. We next screened some selected compounds for their antibacterial activity (Table 2, Supporting Information File 1) against the reference bacterial strains Bacillus subtilis

• . The observed low level of antibacterial activity of the synthesized heterocycles is a good prerequisite for screening them for other types of activity, e.g., anticancer, antidiabetic, etc., because in these cases a negative influence on the microflora of the organism would be decreased [54

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• benzyl improves the in vitro antistaphylococcal activity. In contrast, the incorporation of smaller heterocycles like pyridine and imidazole as well as isosteric benzimidazole instead of the indole moieties lead to a loss of antibacterial activity. Kennedy et al. could synthesize a 2-phenyl derivative

• that showed nanomolar activity against S. aureus [20]. To the detriment of this compound class, all derivatives lose their antibacterial activity in the presence of serum in vitro in serial broth and agar dilution method [16][20]. Even with the use of charged groups as modifiers, serum-protein binding

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• (FP) assay of the selected candidates, the substituted tetrahydrocarbazole 11 (Figure 3) was found to not only completely occupy E. coli SC subsite I with the highest affinity (IC50 = 115 μM) and to inhibit in vitro DNA replication, but also to have antibacterial activity against several Gram-positive

• competition assay. Of the twenty compounds evaluated, five showed Ki values in the high micromolar range, but only vedaprofen, bromfenac and carprofen (13–15, Figure 3) displayed the strongest effects (Ki < 300 μM) [64]. Similarly to the preliminary study by Yin et al. [62] the antibacterial activity of the

• concentrations as low as 44 μg/mL in the case of vedaprofen (13). Again, and in agreement with previous studies, the compounds that most potently inhibited E. coli β-clamp binding also showed the highest level of antibacterial activity, supporting the correlation between inhibition of the sliding clamp and the

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• potent antibacterial activity against Helicobacter pylori and induce growth defects in Escherichia coli and Staphylococcus aureus. Taking inspiration from a methodology used in our total synthesis of natural products, we applied this methodology to access analogues possessing bulky N-substituents

• , and were first isolated by Dekker et al. (1–8, Figure 1) [3]. The authors noted the potent antibacterial activity of these compounds against Helicobacter pylori, which is responsible for the generation of numerous digestive disorders [4]. Furthermore, with the presence of a lipophilic chain in the 2

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• other bacterial species [11]. NDH-2 is absent in mammalian cells and similar to PBPs is associated with the bacterial membrane [12]. Considering the significant antibacterial activity of phenothiazines, in particular the anti-TB activity of 1, and their membrane-associated NDH-2 target we hypothesised 1

• linker is attached to a position in 1 such that the antibacterial activity is not compromised. Based on previous structure–activity studies of 1 by Bate et al., whereby a methoxy group was positioned on the para-position of the phenyl ring of 1 without loss of activity, we hypothesised this may be a

• -up. To determine if the antibacterial activity of the derivatised phenothiazine was retained the MIC of compound 4 was determined in direct comparison to synthesised 1 against Mycobacterium smegmatis (see Supporting Information File 1). M. smegmatis is commonly used as a first assessment for

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• the plant Juniperus excelsa [3][4]. Leopolic acid A is endowed with antibacterial activity against Staphylococcus aureus and Staphylococcus pseudintermedius with a MIC of 16 μg/mL, and against Escherichia coli with a MIC of 128 µg/mL [3][4]. In terms of structural features, this compound contains a 4

• antibacterial activity of compound 1 was tested on Staphylococcus pseudintermedius and Escherichia coli strains chosen as representative of Gram-positive and Gram-negative bacteria. In particular, we demonstrated the ability of compound 1 to inhibit Staphylococcus pseudintermedius strains expressing a multidrug

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• successively partitioned between 60% MeOH (250 mL) and CH2Cl2 (250 mL × 3) and the latter between 90% aqueous MeOH (150 mL) and n-hexane (150 mL × 3). The aqueous MeOH layer, which concentrated the antibacterial activity against Tenacibaculum maritimum, was subjected to ODS flash chromatography (Ø 3 × 7 cm

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• and in a number of other natural compounds that have shown a highly diverse range of biological activity [1][2][3][4][5][6][7][8][9], like the inhibitory activity of inositol monophosphatase [10][11], antitumor [12], antibiotic [12][13], and antibacterial activity [14] and lipoxygenase inhibitor

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

• significant antibacterial activity against Gram-positive bacterial strains [50]. Several other distamycin analogs were synthesized by replacing one or more pyrrole rings with other heterocycles such as pyrazoles [51], benzofurans [52], thiazoles, thiophenes, imidazole and oxazoles [53] in order to establish a

• . Thus, the conjugate 11 was chosen for further development as an anti-lung cancer therapeutic. In the similar fashion, the same group investigated the correlation between DNA binding and antibacterial activity shown by these novel distamycin alkene-containing analogs (MGB-BP-3, 12 and 13, Figure 4

• heterocycles, resulting in lowering the binding affinity and specificity [121]. Arya et al. reported a series of Hoechst 33258 based mono- and bisbenzimidazole derivatives and their E. coli DNA topoisomerase I inhibition, binding to B-DNA duplex, and antibacterial activity has been evaluated [122]. It has been

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• hydrochloride 5 and the remaining compounds. In the case of antibacterial properties, N-ethyl derivative 11 is the most active among the all tested compounds. Moreover, derivative 11 acts against all tested Gram-positive bacteria. An introduction of an additional ethyl group worsens the antibacterial activity