Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• (Figure 12). Studies of the TPA properties demonstrated that some of these dendrimers outperform the TPA cross-section response of quantum dots, while having a much lower intrinsic toxicity, as being composed or organic matter instead of heavy metals. The grafting of water-solubilizing functions on the

• deciphering mechanism of action of anticancer compounds, and recently for safer photodynamic therapy. In view of the results already obtained, there is no doubt that other biological properties of these fully organic “nanodots” can be foreseen, thanks to their low toxicity, large color modularity, and high

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• of these technologies has been partially hampered by the high cost and toxicity associated with Pd, in addition to the difficulty encountered when attempting to remove this metal from product mixtures. Therefore, cupper as low-cost, earth-abundant and readily available transition metal has emerged as

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

• from Heydenia cf. alpina strain 824. Acknowledgements We are grateful to Tobias Meinert and Max Schirp Schönen (RWTH Aachen, Aachen, Germany) for 3D modeling of the FIND and to Tobias Benkel (University of Bonn, Bonn, Germany) for performing of the toxicity assays.

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• photoredox catalytic behavior, transition metal complexes have disadvantages, including high costs due to limited availability, toxicity [22][23] and polluting properties [24]. This thwarts the principally “green” concept of photoredox catalysis. In order to avoid transition metals and enhance the

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• treatment of rheumatoid arthritis (RA) [31], systemic lupus erythematosus (SLE) and skin allograft rejection [32]. Despite the promising biological activities of triptolide, the narrow therapeutic window and multi-organ toxicity hindered greatly its clinical progress. Reports have shown that triptolide

• could cause reproductive toxicity [33], nephrotoxicity [34], hepatotoxicity [35], myocardial damage [36] and gastrointestinal tract symptoms [37]. In order to overcome the above issues and find derivatives with good drug-like properties, extensive total syntheses and structure modifications have been

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

• micromolar range and up to the tested concentration of 50 µM, 50% cell death was only reached for HEK 293T and LNCaP after 72 h of treatment. Moreover, we also did not detect toxicity of compound 1 in primary and transformed cell lines. Based on these differences from thapsigargin and compound 2, it seems

• to 75% (statistically not significant) was also recorded when rat primary macrophages were incubated with 1000 pg·mL−1 LPS + 40 µM compound 5. However, no toxicity was observed for the combination of LPS + dansyl amide at the same concentration. Immunomodulatory [26] and anti-inflammatory [27

• , USA). The treated or untreated cells (DMSO as a vehicle) were cultured for 24 h and plates were maintained at 37 °C, 5% CO2, in a humidified Heraeus incubator. Stock solutions of compound 1 and 5 were prepared 100 mM in DMSO. For the cultivation of macrophages and assessment of toxicity and NO level

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

• on the basis of the dissociation of host–guest interactions between β-CD and BM. Cellular toxicity of drug-loaded supramolecular self-assemblies The biocompatibility of drug-free supramolecular self-assemblies is of crucial importance for the further use of these materials as drug carriers. Herein

• 240 μg/mL, indicating a good biocompatibility. An MTT assay was then conducted to evaluate the potential of supramolecular self-assemblies as intelligent drug release carriers within a biological environment. The cellular toxicity of DOX-loaded FSSAs and free DOX·HCl against PC-3 cells was further

• acidic conditions into spherical supramolecular self-assemblies with smaller size. The morphology transitions can be utilized to realize a two-stage drug release. The uptake of the DOX-loaded supramolecular self-assemblies performed efficiently and the cellular toxicity through inhibiting cell

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• TLR2 receptor, whereas MDP lacks TLR2-agonistic activity [10]. PGM and MDP have similar immunostimulating activity and they are reduced in comparison to the potent complete Freund’s adjuvant which is used as golden standard for adjuvant activity [11]. However, strong toxicity of complete Freund’s

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

• . In this study, the influence of substitution in the benzofuranone ring on the UV–vis spectrum is explored, as well as an initial screening of their toxicity and a qualitative preliminary study of their potential to act as fabric dyes. Keywords: aurone; dyeing; dyes; substitution effect; toxicity; UV

• sake of high purity, so yields should not be considered optimized. Spectral and toxicity studies With the desired compounds in hand, their UV–visible spectra were recorded at concentrations between 29 and 44 μM in acetonitrile (Figure 3 and Table 1). While not all substituents were prepared at every

• definitely increase this value by roughly 50%). While these results on the impact of the benzofuranone portion of aurones on their optical properties are interesting, if one were to think about using them as dyes, toxicity is also an important consideration. Generally, aurones are considered to be relatively

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• ] but these molecules reveal low absorption coefficients over the visible range. Furthermore, they contain a rare and a relatively high-cost element (Ru) and their plausible toxicity restrains their development at the industrial level. For these reasons, in the last decade, metal-free organic dyes based

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• in toxicity and fits to the tenets of green chemistry. Zinc in the form of its salts, complexes (chelated by mono/di/tri/tetradentate ligands), oxides and sulfides proved to be a promising and active catalyst for organic chemists in both homogeneous as well as heterogeneous reaction systems [23][59

• systems based on zinc with excellent activity has been designed and used. The role of iron in synthetic chemistry Iron being the most abundant heavy element on earth with low biological toxicity along with cost economy and high reactivity was explored by Kharasch and Fields in the 1940s and Tamura and

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

• core structure, 1 only has one stereocenter as compared to seven in AbC. Furthermore, the benzylated derivative 2 was also envisioned to mimic the favorable toxicity profile observed for atrop-O-benzyl-desmethyl-abyssomicin C (Figure 1) [10]. Here we present the synthesis and biological evaluation of 1

• , no further investigations related to the conserved mode of action or toxicity were performed. Conclusion We have described the synthesis and antibacterial activity of two new truncated derivatives of AbC. Previous work indicated that the three methyl groups of AbC were not required for activity [10

Reversible end-to-end assembly of selectively functionalized gold nanorods by light-responsive arylazopyrazole–cyclodextrin interaction

• Maximilian Niehues,
• Patricia Tegeder and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2019, 15, 1407–1415, doi:10.3762/bjoc.15.140

• the complete surface because of its cell toxicity [17], hence strategies for replacing this coating are desirable. Host–guest chemistry is a supramolecular interaction that is tailor-made for self-assembly due to its lock–key mechanism and has been applied in our and other groups to various

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• did not reveal the presence of any elimination product, while the negative mass spectrum showed only the pseudomolecular ion at m/z 145 corresponding to the [M − H]−. The toxicity of compounds 8 and 11, compared to commercial BPA, on cell viability, was evaluated on human primary fibroblasts. The

• cells were treated (24–72 h) with increasing concentrations (1–100 μM) of each compound, and cell viability measured by MTT assay. No toxicity was measured at all concentrations and times considered (see Supporting Information File 1), indicating that all compounds under evaluation are biocompatible and

• ester ring opening, while compound 11 demonstrated to be stable. The two compounds showed no toxicity on human primary fibroblasts. Further studies will be conducted to determine the cellular uptake of compounds 8 and 11. Structure of boronic acid analogues (for clarity, sugar numbering has been

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• molecules [27], including some amino acids [28] and proteins [29]. They are also biocompatible: compared to other types of macrocyclic molecules such as cyclodextrins and cucurbiturils (which are also water soluble), p-sulfonatocalix[n]arenes do not exhibit any toxicity, which makes them applicable in

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• lateritium (causal agent of chlorotic leaf distortion in sweet potato) and Fusarium virguliforme (causal agent of sudden death syndrome in soy bean), without exerting in vitro toxicity on mammalian cells. Another interesting result came out from the comparison of the biological activity between homologous

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• cytotoxic agent. The problem of concomitant toxicity to healthy cells has been circumvented by attaching a short peptide (His-Ser-Ser-Lys-Leu-Gln-Leu) to a tether at TG’s C-8 position (1b). This modification renders the inhibitor inactive [3]. Prostate cancer cells produce on their surface the serine

• synthetic route to BHQ analogues with a tether that could serve as the basis for future efforts aimed at the attachment of deactivating peptides. The rationale is analogous to the Denmeade group’s strategy for circumventing TG’s toxicity to healthy cells by selective transesterification of the ester group

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• Discussion Aliphatic polycarbonates are found in many biomedical applications since they have many desirable properties such as high biocompatibility, easy degradation, good mechanical properties, and low toxicity [21][22][23]. Many synthetic methods have been developed, and the chain-growth ring-opening

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

• described above, nitroxides are not toxic to normal host cells and exhibit toxicity only to tumor cells. Thus, nitroxides are ideal candidates as anticancer therapeutic agents. Based on this knowledge, the cytocidal effect of the radical released from compound 2a on lung cancer cells was tested in vitro, in

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• not show any toxicity against L6 cells (a primary cell line derived from rat skeletal myoblasts). These results contribute to a better understanding of artemisinins mechanism of action. Keywords: artemisinin; biomimetic synthesis; Diels–Alder reaction; malaria; peroxides; Introduction The isolation

• against the drug-sensitive P. falciparum NF54 strain as described previously [14]. We found them to be inactive. In addition, 2 did not show any toxicity against L6 cells (a primary cell line derived from rat skeletal myoblasts). In both assays the highest concentration used was 100 μg/mL. Conclusion In

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

• (Ewing`s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chemically transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic

• very potent, mostly cytotoxic drug molecules while avoiding or at least limiting the off-target toxicity that would be characteristic for the stand-alone cytotoxic drugs. Currently, four therapeutic ADCs are approved, e.g., with brentuximab vedotin and trastuzumab emtansine as the first ones on the

• cells’ membrane by unspecific, receptor-independent pathways, not discriminating between normal and transformed cells. For that reason it is very difficult to adjust a practicable therapeutic window for these toxins. All the more, it is important to mask the high toxicity of tubulysin A and tubugi-1

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• lower toxicity, air sensitivity and lower costs [34]. A huge repertoire of organocatalyzed reactions have been published in recent years with high efficiencies and selectivities [29][33][35][36][37][38][39]. Proline as a natural amino acid is a perfect example of an organocatalyst. Both enantiomers are

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

• antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant P. aeruginosa

• effective than the clinically used antibiotic tobramycin in eradicating biofilms. Although cisplatin is highly toxic for intravenous applications, we showed that it has low toxicity when applied topically to wounds, as 25 mM (0.75 mg mL−1) did not have adverse effect on wound healing. This meant that higher

• doses (5–10 × MIC) of cisplatin could be safely used for topical applications. Given the low topical toxicity of cisplatin, it may be utilized as an attractive therapeutic agent for prevention and treatment of P. aeruginosa biofilm infections. Materials and Methods Bacterial strains and culture media

Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region

• Aude-Héloise Bonardi,
• Frédéric Dumur,
• Guillaume Noirbent,
• Jacques Lalevée and
• Didier Gigmes

Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282

• chemistry. Thanks to the development of photoredox catalysts of polymerization, a drastic reduction of the amount of photoinitiators could be achieved, addressing the toxicity and the extractability issues; high performance initiating abilities are still obtained due to the catalytic approach which

• catalysts For some specific applications, it can be essential to develop metal-free systems because of potential toxicity, storage stability or bioaccumulation of metal for example. Organic photoredox catalysis has been largely studied in the past few years and is the topic of many reviews [17][40][45][49

• conditions tested. The choice of the photoredox catalyst has also to be done regarding the application: final toxicity, choice of the device to perform the polymerization (light irradiation, under air or not…), price of the formulation, etc. For both free radical and cationic polymerizations, only a very

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

• -positive pathogens such as methicillin-resistant S. aureus and S. pneumoniae but also Gram-negative bacteria strains such as P. aeruginosa and A. baumannii (MIC ≤ 3 μg/mL and ≤51 μg/mL, respectively) [95]. In spite of the efficiency of the bis-aminoguanidine derivative 42, unfortunately, its toxicity was

• not display toxicity to mammalian cells. Even though the NusB/NusE interaction is still in its infancy, and further investigations are needed to both elucidate off-target effects and apparent preferential inhibitory activity against Gram-positive pathogens, the identification of promising small