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

• , sponges, molluscs and other fungi as well and possess a wide range of bioactivities [24]. The drimane sesquiterpenoids isolated from Aspergillus spp. have exhibited in vitro anti-inflammatory [5] and antiviral [22] activities as well as cytotoxicity against several mammalian cell lines [4][16][22

• activity observed for 2, 3, 6 and 8. Compounds 2, 5, 8, 9 and 10 exhibited low levels of cytotoxicity against the four mammalian cell lines tested, while 3, 6 and 7 were considerably more cytotoxic. Notably, 4 showed strong activity against the mouse myeloma NS-1 cell line, but no activity against the

• activity against human and murine tumour cell lines. This suggests that the regioisomeric lactone moiety could play an important role in the observed cytotoxicity. Interestingly, 3 (SF002-96-1 [4]) was previously shown to inhibit survivin, which is a member of the inhibitor of apoptosis (IAP) family and a

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

• cell viability assay on human fibroblasts (Detroit 551 cell line) was performed for compounds 9e and 9g in order to observe their eventual cytotoxicity to normal cells (see Supporting Information File 1, assay 4). The concentration range tested was 6.25 to 200 µM for 9e and 9.38 to 300 µM for 9g

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• preliminarily evaluated for anticancer activity towards HeLa cells. The administration of the analogues caused a significant decrease in the proliferation of HeLa cells. Furthermore, one of the analogues showed a maximum cytotoxicity with a minimum GI50 value of 2.5 µg/mL and the generation of reactive oxygen

• clearly the truncated analogue 11g is less effective. Loss of cell viability by LDH assay LDH assays quantitatively measures lactate dehydrogenase (LDH) released into the media from damaged cells as a biomarker for cellular cytotoxicity [35][36]. Hence, to further characterize compound-induced HeLa cell

• a minimal effect of cytotoxicity (≈9.1% necrotic as well as apoptotic cells, respectively), by observing the morphology of the cells under a microscope at a concentration of 15 μg/mL. ROS generation study by DCFDA (2′,7′-dichlorodihydrofluorescein diacetate) by FACS (fluorescence-activated cell

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• hydrolysis of the fatty acid ester bonds of lysophospholipids [31][41]. Moreover, cyclooctatin (5) was shown to be effective against Plasmodium falciparum with an IC50 of 7.14 µg/mL along with very low cytotoxicity [42]. CotB2 belongs to the class of cyclopentane-forming diterpene synthases [46], a class of

• cytotoxicity [82]. Further, thunbergol (18) is reported to repel aphids within 48 h by 70%, if wheat seedlings are topically treated with a 0.25% (w/w) solution in ethyl acetate, compared to untreated plants [25]. During application in agriculture a negative impact on useful insects, like bees, should be

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• only nano- or picomolar amounts of the radiopharmaceutical compound are needed, medical applications of fluorescence dyes (e.g., fluorescence-guided interventions) require larger amounts of material. Therefore, cytotoxicity testing is necessary for our proposed bimodal imaging agent 16 and its

• , without dye: 0.32 ± 0.06 divisions per cell, for division duration see Figure S7, Supporting Information File 1). These results are supported by cell count and confluency analysis (Figure S9, Supporting Information File 1). In summary, we conclude that dye 15 does not show any significant cytotoxicity in

• undisturbed cell proliferation in U2OS cells incubated with 1 µM of dye 15 for 1 h compared to untreated U2OS cells are given. Supporting Information File 442: Experimental and analytical data, spectra, live cell imaging and assessment of cytotoxicity. Supporting Information File 443: Independent experiment

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• the appropriate test organism was significantly inhibited compared to a negative control; total inhibition: no growth at all in the appropriate zone. Benzylpenicillin (1 mg/mL MeOH), streptomycin (1 mg/mL MeOH) and miconazole (0.5 mg/mL DCM) were used as positive controls. Cytotoxicity assay HEK293

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• temperatures, as well as low levels of cytotoxicity against mouse fibroblast 3T3 cells [191]. With these characteristics in mind, the outlook for these hydrogels having therapeutic applications is promising, with further optimisation [236]. Pentafulvenes have also been used to prepare monomers for ring-opening

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• ] and was also found to be cytotoxic with localization to the endoplasmic reticulum [8]. The cytotoxicity of compound 2 prompted the preparation and evaluation of compound 2 conjugates with porphyrins [9] and steroids [10] for targeted uptake of compound 2 into cancer cells, and the conjugates showed

• interesting biological effects including antimycobacterial effects [10]. Nevertheless, cytotoxicity posed a considerable limitation for the utilization of compound 2. It was, however, soon found that compound 2 may be modified in such a way that its cytotoxicity is reduced while the immunobiological

• properties are retained [11]. Contrary to compound 2, compound 1 inhibits NO production and synthesis of IL-1β and INF-γ [12]. Although its structure was already elucidated in the 1970s [13], the information on cytotoxicity of compound 1 is very limited [12] and its intracellular localization and mechanism

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• , the biocompatibility of β-CD-BM2-based FSSAs towards PC-3 cells was investigated with different concentrations after incubation for 48 h. The result did not show any cytotoxicity against PC-3 cells (Figure 5a). The viability of PC-3 cells could reach 84% even when the concentration of FSSAs was up to

• investigated. As shown in Figure 5b, DOX-loaded FSSAs displayed reduced cytotoxicity against PC-3 cells in comparison with free DOX·HCl. The in vitro half-maximal inhibitory concentration (IC50) values of DOX-loaded FSSAs and free DOX·HCl after incubation for 48 h were 1.44 and 0.91 μg/mL, respectively. The

• results further certified that the fast intracellular drug-release process of DOX-loaded FSSAs provided a large intracellular drug dose and high cytotoxicity. All these results suggested that DOX-loaded FSSAs presented a potential application in controlled drug delivery. Intracellular uptake of drug

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• well as its longer term retention and photostability are required. Conclusion In conclusion, the benzofuranone portion of the aurone skeleton does have a definite impact on both the UV–vis spectral and cytotoxicity properties of aurones. Interestingly, the position of the substituent was often more

• displays a significant blue shift by roughly 40 nm. With respect to toxicity, halogens were the least toxic substituents, displaying the lowest cytotoxicity when at the 6- or 7-positions. Hydroxylation or substitution at the 4-position invariably lead to higher cytotoxicity, though often times no worse

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

• (+)-deoxocassine ((2S,3S,6R)-190a) and (+)-spectaline ((2S,3S,6R)-190b) as already described. (+)-Microgrewiapine A ((2R,3S,6R)-194a) [107] and (+)-microcosamine A ((2R,3S,6R)-194b) [108] have recently been isolated and exhibited interesting biological activities, for example cytotoxicity [107]. The total

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

• . Accordingly, structure–activity relationship (SAR) studies have been performed, which indicate that benzylation of the hydroxy group and the complete demethylation of the core structure of AbC retain the antibiotic activity towards MRSA while simultaneously decrease cytotoxicity towards various human cell

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• cytotoxicity [9]. However, it is of great importance to obtain all stereoisomers for the study of biological activity. Therefore, the development of methods for the asymmetric synthesis of polyfunctional sulfones is valuable. The most notable of them are Ag- and Cu-catalyzed 1,3-dipolar cycloaddition reactions

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• (0, 10, 100 μg mL−1) and further incubated for 4 h under the same conditions. Without exposure to light, 2a itself exhibited slight cytotoxicity based on trypan blue exclusion, and ≈80–90% living cells remained in the medium containing of 100 μg mL−1 of 2a (Supporting Information File 1, Figure S8

• 2a induced cancer cell death in vitro, although no in vivo study was performed because of the low water solubility of 2a. At this point, we cannot rule out generate of ROS by photosensitization of the chromophore in the presence of O2 for the cytotoxicity. Conclusion In the present study, novel caged

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• conditions and microscopy settings resulted in a bright staining for Ac4GlcNCp and Ac4GalNCp well over that of the negative control (Figure 5). These results were confirmed by flow cytometry (Figure 4 and Figure 5). Interestingly, we did not observe cytotoxicity of Ac4GlcNCp up to a concentration of 100 μM

• . Comparison of glucosamine and galactosamine derivatives Having proven the suitability of Ac4GlcNCp for MGE, we next compared it with Ac4GlcNCyoc. First, we investigated the staining intensity on the cell surface by confocal fluorescence microscopy. Owing to the cytotoxicity of Ac4GlcNCyoc, a concentration of

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• cytotoxicity [3]. A photoreactive derivative of the cytotoxic jasplakinolides, geodiamolides [4][5], or seragamides (2–6, seragamides A–E) [6] could also enable the search for additional targets in the cell, including proteins involved in transport or even membrane components. For this purpose, the 2

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• to increased fluorescence quantum yield (74%) in THF solution. The compounds exhibit low cytotoxicity and as such are useful for the cell labelling studies in the future. Keywords: 7-deazapurines; fluorescence; nucleophilic aromatic substitution; purines; push–pull systems; pyrrolo[2,3-d]pyrimidines

• lines – luminal A breast cancer cell line MCF7 and triple negative breast cancer cell line MDAMB231. The results were compared with those obtained on normal breast epithelial cell line (MCF-10A). All compounds showed low cytotoxicity on all tested cell lines (for Figure S81 see Supporting Information

• File 1). Bearing in mind fluorescent properties and low cytotoxicity of the newly obtained compounds, we tested their potential application in cell staining. The preliminary experiments revealed that the compounds went through the cell membrane after 1 h or 2 h incubation period and localized uniformly

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• Pharmaceuticals GmbH, Leberstr. 20, A-1110 Vienna, Austria 10.3762/bjoc.15.11 Abstract Tubugi-1 is a small cytotoxic peptide with picomolar cytotoxicity. To improve its cancer cell targeting, it was conjugated using a universal, modular disulfide derivative. This allowed conjugation to a neuropeptide-Y (NPY

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• , homogenized in 1 mL 0.9% NaCl, serially diluted and plated on LB agar plates for incubation at 37 °C overnight. Colonies on the plate were counted and CFU mL−1 was tabulated. Experiments were conducted in triplicate, and results are shown as the mean ± s.d. RAW264.7 macrophage cytotoxicity assay The murine

• . aeruginosa was correlated with acute cytotoxicity to host epithelial cells and immune cells such as macrophages and neutrophils [38]. As we demonstrated that cisplatin treatment was able to reduce the T3SS of P. aeruginosa, we further tested the ability of cisplatin in attenuating the acute cytotoxicity of P

• between groups. *P ≤ 0.05. (B) Cisplatin treatment reduced cytotoxicity of P. aeruginosa PAO1 against mouse macrophage cells. Means and s.d. from triplicate experiments are shown. Student’s t-test was performed for testing differences between groups. *P ≤ 0.05. P. aeruginosa biofilm killing assay by

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• against E. coli TolC, and it was the only compound that showed moderate cytotoxicity on a human cancer cell line. The close similarity of NAMEs, NAVMEs, and NAGMEs to AHLs might indicate a function as signalling compounds, although experiments with NAMEs and AHL reporter assays did not reveal any activity

• (minimum inhibitory concentration, MIC, in µg/mL) and cytotoxicity (minimum inhibitory concentration, MIC, in µg/mL) of selected NAVME, NABME and NAGME derivatives. Minimal inhibitory concentration and IC50 values for cytotoxicity in μg/mL. Supporting Information Supporting Information File 428

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• molecule [34]. This autoinducer has been described to mediate iron acquisition, cytotoxicity, outer-membrane vesicle biogenesis, and to exert host immune modulatory effects [34][35]. Interestingly, PQS as well as HHQ are able to interfere with nuclear transcription factor-κB and hypoxia-inducible factor 1

• by pqs QS, pyocyanin is one of the most prominent. This redox-active pigment is responsible for the greenish-blueish colour of P. aeruginosa cultures. It seems that generation of reactive oxygen species is a major mechanism of pyocyanin cytotoxicity [41]. This tricyclic compound is known to induce

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• plasma and liver microsomes, absence of cytotoxicity, and excellent oral bioavailability in mice. 4. Direct toxin inhibition Numerous bacteria secrete toxins that are responsible for acute virulence. Various small molecule and antibody approaches target the inhibition of bacterial toxins in order to

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• was inactive against MRC-5 normal embryonic lung cell (0% cytotoxicity at concentration of 50 μg/mL). Molecular docking studies Molecular docking studies [15] were performed to study the binding mode and interactions of the synthesized compounds with AChE. A crystal structure of recombinant human

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• melanoma cells was increased by [4Lys(Ac)]-GnRH-III(Dau=Aoa), while the GnRH-III(Dau=Aoa) and [4Lys(Bu)]-GnRH-III(Dau=Aoa) decreased this activity. Conclusion: Internalization and cytotoxicity of the conjugates showed that GnRH-III peptides could guard Dau to melanoma cells and promote antitumor activity

• . [4Lys(Bu)]-GnRH-III(Dau=Aoa) possessing the butyryl side chain acting as a “second drug” proved to be the best candidate for targeted tumor therapy due to its cytotoxicity and immobilizing effect on tumor cell spreading. The applicability of impedimetry and holographic phase imaging for characterizing

• electrode surface, makes this impedimetric assay sensitive enough for cytotoxicity experiments [36]. In the event of a cytotoxic compound, the cells detach from the electrode surface and a drop in the impedance – given as Cell index values – could be observed. According to the time-course study, the

Correction: 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. 2018, 14, 2394–2395, doi:10.3762/bjoc.14.215

• benzenoid derivatives; cytotoxicity; marine alga-derived fungus; Paecilomyces variotii; TDDFT-ECD calculation; The authors wish to rename compounds 1 and 2 (shown in Figure 1 of the original article [1]) as varioloids C and D, respectively (Figure 1), as the synonyms varioloids A and B have already been