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

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. A second generation total synthesis of the antibiotic elansolid B1 (2) and the first synthesis of elansolid B2 (3) are reported. In contrast to previous work, the (Z,E,Z)-triene at C10–C15 was assembled by using

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• obtained were evaluated for their antibacterial activity and several of them demonstrated a weak antimicrobial effect, but for most of the compounds a 30–50% increase in biomass of Gram-positive strains (mainly B. subtilis) compared to control was observed. Keywords: 3-amino-5-methylisoxazole; 5-amino-N

• -aryl-1H-pyrazole-4-carboxamides; antibacterial activity; Groebke–Blackburn–Bienaymé reaction; isocyanide Ugi reaction; Introduction An intensive progress in pharmaceutical and medicinal chemistry, as well as in the generation and improvement of medicinal technologies has led to defeating a wide scope

• compound 9e (Figure 5). Antibacterial activity The antibacterial activity of compounds 4, 6 and 9 (Table 7) was studied (see Experimental part in Supporting Information File 1 for details) against reference bacterial cultures: Bacillus subtilis (strain 1211), Staphylococcus aureus (strain 2231) (Gram

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• antibacterial activity against Escherichia coli and Bacillus subtilis, and antifungal activity against Aspergillus niger and Penicillium notatum. Among the synthesized series of 1-indanone derivatives 64, the highest antibacterial activity was exhibited by derivatives 64k and 64l, whereas the most potent

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

• -positive bacteria, including resistant strains [2][9][20] and Mycobacterium species [21]. No activity was observed against Gram-negative bacteria (except for Neisseria gonorrhoeae), fungi or yeast [9]. The antibacterial activity arises through inhibition of cell wall synthesis [22] by prevention of

• bacteria [7] with the primary cellular target deduced to be bacterial cell wall synthesis [34]. Extensive derivatisation of both mannopeptimycin α (12) and β (13) was undertaken to improve the antibacterial activity of the parent natural products (highlighted in blue, Figure 6). An array of ether [35][36

• ], halogenated [36], acetal [37][38][39], benzoxazole [40], thiobenzoxazole [40], ester and carbonate [41] analogues were synthesised and evaluated for antibacterial activity. Only the semisynthetic derivatives possessing hydrophobic groups on the terminal sugar moiety (green) exhibited comparable antibacterial

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• prolific source of bioactive secondary metabolites of diverse structures, including, for example, semiviriditoxin derivatives with antibacterial activity [3], cornexistin and hydroxycornexistin with herbicidal activity [4], and paecilocins with antibacterial activity [5]. During our ongoing effort to

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds

• residue, which in turn, is connected to the ureido dipeptide L-Phe-L-Val. The compound showed antifungal and antibacterial activity against Mucor hiemalis and Staphylococcus aureus with a MIC of 32 and 16 μg/mL, respectively [2]. Compounds containing the isomeric 2,4-pyrrolidinedione ring system (tetramic

• µg/mL for both molecules (see Supporting Information File 2 for details). The antibacterial activity shown by both compounds suggests that they can be considered as promising candidates for further developments. Conclusion In conclusion, leopolic acid A was obtained for the first time in a 11-step

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• groups. Besides a common antibacterial activity, many tetronates also have further attractive bioactivities that triggered interest in their research [139][140]. Tetronates and their biosynthesis have recently been extensively reviewed and a classification based on structural characteristics was devised

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• (alternatively named lantipeptides [44]) are large bacterial RiPPs, and the first member to be reported was nisin (Figure 4A) from Lactococcus lactis in 1928 [45]. Many members of this family have antibacterial activity and these are termed lantibiotics [46]; nisin itself is used as a food preservative as it

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• . Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms. Keywords: antibacterial activity; dithiocarbamates; dithiolium salts; flavonoids; SAR studies; Introduction The extensive use of antibiotics in human treatment and agriculture has led to the development

• nature of the dialkylamino moiety at the 2 position of ring D. After the best correlation between the antibacterial activity and the nature of the dialkylamino moiety had been identified as the N,N-diethylamino group, this substituent was maintained, while the structure–activity study was extended to

• the heterocyclic ring in 5a. In vitro antibacterial activity The promising results obtained in our previous studies [13][27] prompted us to investigate to what degree the amino moiety and the two halogen atoms bound to tricyclic flavonoids of type 5 influence their antibacterial activity. This study

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• 16 was neither a good substrate nor an inhibitor of this enzyme, hence explaining its lack of antibacterial activity towards E. coli. On the other hand, compound 16 was found to inhibit the growth of Plasmodium falciparum with an IC50 value of 60 ± 11 μM (n = 3) in the absence of pantetheinase

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

• activity against Gram-positive bacteria was observed, but it displayed pronounced antibacterial activity against P. aeruginosa. This remarkable finding distinguishes the mureidomycins, pacidamycins, sansanmycins and napsamycins from other nucleoside antibiotics. On the other hand, caprazamycin B shows good

• μg/mL and 4 μg/mL. Derivatives with unnatural D-stereochemistry in the pentadecyl glycine motif possessed a similar antibacterial activity (potency within factor 2). Truncated analogues lacking the L-valine urea terminus (Cbz-protected 92d and N-terminally unprotected 92e) showed only a minor loss of

• central leucine unit and the terminal truncation had no crucial effects on the antibacterial activity (Table 2). Truncated derivatives 92f–h (Figure 10) without the L-valine urea terminus contained L-ornithine (L-Orn, 92f), L-arginine (L-Arg, 92g) and L-methionine (L-Met, 92h), respectively. They were

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

• 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

• a restricted prey spectrum [82]. Regarding the available information on the chemistry of predatory myxobacteria, it seems likely that every strain has the potential to produce at least a single class of natural products with potent antibacterial activity. The high recovery rate of myxovirescins and

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• of myxovalargin (1), a secondary metabolite from Myxococcus fulvus with antibacterial activity [14][15], we report on copper-mediated cross-coupling chemistry to create peptide fragments bearing dehydrovaline and dehydroisoleucine. We faced difficulties to use the reported conditions for the C–N

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• -glucopyranoside (vanillyl β-D-glucoside, 1) isolated from the exocarp of Juglans mandshurica Maxim showed antibacterial activity [1]. A wide range of pharmacological effects, e.g., anti-oxidant, anti-inflammatory, anticancer, hepatoprotective, cardioprotective, neuroprotective, antidiabetic, and antiviral

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• binding affinity [21], inhibition of hepatic cholesterol [22], inhibition of aldose reductase [23], antiproliferative [24], antiviral, cytotoxic [25], antifungal [26], anti-HIV [27][28][29] and antibacterial activity [30]. Although rare, there are a few natural products, for example, melanervin (5), a