N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• released by microorganisms into their surrounding extracellular environment to chelate iron and selectively import it into the microbial cells [12][13]. It has been suggested that the release of siderophores by soil-dwelling pseudomonads give them an ecological edge by creating an iron-deprived environment

• determined using two-fold serial dilutions of the compound in media, carried out in 96-well plates in quadruplicate. Parasites were counted using a CASY TT Cell Counter. Alamar Blue viability assays were performed, whereby cells were incubated with the compound in serial dilution (specific details for each

• bathocuproine sulfonate, 1.5 mM ʟ-cysteine, 1 mM hypoxanthine, 0.2 mM 2-mercaptoethanol, 1 mM sodium pyruvate and 0.16 mM thymidine). Cells were added to the compound (2-fold serially diluted in HMI-9 growth medium) to a density of 1 × 103 cells/well and incubated at 37 °C with 5% CO2 for 72 hours, after which

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• -PfATP4 activity would be required to definitively assess the tolerability of tertiary alkylamines at position 8. Whilst compounds 1, 2 and 4–12 showed no cytotoxicity against HEK293 cells at the top concentration tested (80 µM), for those compounds with concomitant antimalarial activity (1, 10–12), their

• purified by the Davis group [8]. In vitro antiplasmodial image-based assay Plasmodium falciparum 3D7 were cultured in RPMI1640 (Life Technologies, Camarillo, CA, USA) supplemented with 2.5 mg/mL Albumax II, 5% AB human serum, 25 mM HEPES, and 0.37 mM hypoxanthine. Human red blood cells (RBC) (O+) were

• using an Opera PhenixPlus™ High Content Screening System (PerkinElmer, Waltham, MA, USA). Images were analysed using the Harmony software (PerkinElmer, Waltham, MA, USA). In vitro cytotoxicity assay Human embryonic kidney (HEK293) cells were maintained in DMEM (Life Technologies, Camarillo, CA, USA

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• in medicinal chemistry. For example, racemic compound 1 (Figure 1) was evaluated for its cytotoxicity against human breast cancer cells (MCF7) in comparison to the standard doxorubicin and exhibited excellent activity against the MCF7 cell line [12]. The optically active compound 2 also showed

• activity against Huh7.5-FGR-JC1-Rluc2A cells, which carry HCV gt 2a [13]. Therefore, developing asymmetric reactions that simultaneously form a carbon–nitrogen bond and construct a chiral center is of great importance. Although a relatively large number of asymmetric allylic amination reactions using

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen, 37075 Göttingen, Germany 10.3762/bjoc.21.66 Abstract Phenylazopyrazole photoswitches proved to be valuable structural motifs for various applications ranging from materials science to

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• isoforms of NOS named according to their site of existence and include inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) [4]. For example, upon bacterial infection in humans, immune cells express iNOS which promotes the release of NO causing inflammation [5] and NO supports defense to

• clear that overproduction of nitric oxide (NO) by the iNOS enzyme causes inflammation-related diseases. Moreover, large quantities of nitric oxide (NO) are released when RAW 264.7 cells are stimulated by lipopolysaccharides (LPS) [5][26]. Consequently, nitric oxide (NO) production in LPS-stimulated

• -position of that heterocyclic core in compound 5e resulted in a dramatic increase in the NO inhibitory capability. More importantly, all studied compounds 5a–e did not show cytotoxicity to macrophage cells; 90.35–95.74% cells survived at the concentration of 100 µM of 5a–e (Table S3 in Supporting

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• that controls reaction selectivity by adjusting voltage or current [13]. Simple synthetic systems in electrochemical methods are limited to electrodes, cells, electrolytes, and power supplies. Today, in addition to the above, light, metallic, and organic catalysts are also used to increase the

• Electrochemical reaction cells When a redox reaction occurs indirectly, chemical energy is transformed into electrical energy. A device that facilitates this conversion is known as an electrochemical cell. Electrochemical reaction cells are divided into two primary categories: galvanic (voltaic) and electrolytic

• . They consist of two electrodes – anode (where oxidation occurs) and cathode (where reduction occurs) – immersed in an electrolyte. Galvanic cell The redox reaction occurs spontaneously in these cells, converting chemical energy into electrical energy. The potential difference between the two electrodes

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• protocol [41], the fluorescent GFP (green fluorescent protein)-expressing strain PKL1162 was applied to mannan-coated microtiter plates. In this assay, fluorescence intensity correlates with the number of adhered bacterial cells. The photoswitches 1–5 (cf. Figure 1) were used as inhibitors of bacterial

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• with an electrophilic handle for the covalent attachment of the surrogate to the RNA. The resulting irreversibly tethered dye–RNA complexes have opened up new avenues for RNA imaging in live cells. Here, we report the syntheses of such modified HBC530 ((4-((2-hydroxyethyl)(methyl)amino)benzylidene

• aptamer (FLAP) in the family of “RNA mimics of GFP”, called Spinach [3]. This aptamer was used to study intracellular RNA dynamics in living cells and was the starting point for a series of in vitro selected FLAPs, e.g., Corn [4], Chili [5], Mango [6], Pepper [7], Clivia [8], and Okra [9]. All known FLAPs

• (pulldown of circular Pepper RNA from total RNA of HEK 293T cells) see reference [11]. Supporting Information Supporting Information File 26: Experimental, characterization data and copies of NMR spectra. Funding This work was funded in part by the Austrian Science Fund FWF [P31691, F8011-B] and the

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• designed in the context of cancer therapy [1], which combines the precision targeting of monoclonal antibodies (mAbs) with the therapeutic effects of cytotoxic drugs [2]. The ADCs are thus designed to deliver potent cytotoxic agents selectively and directly to cancer cells while minimizing damage to

• healthy tissues. Notably, ADCs have started to enter clinical trials for non-oncology applications as well [3]. The importance and value of ADCs are several fold: Precise targeting: ADCs specifically recognize their target cells because of their antibody component. This minimizes collateral damage to

• healthy tissues, reducing side effects compared to traditional chemotherapy. Enhanced potency: By delivering cytotoxic payloads directly to tumor or other target cells, ADCs achieve higher drug concentrations at the site of action. This potency enhances therapeutic efficacy. Treatment of refractory

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• , epidermoid carcinoma A431, ovarian carcinoma SKOV-3, and breast cancer MCF-7 cell lines. Compounds 2 and 3 exhibited significant cytotoxicity against all the tested cells. Some of the semisynthetic derivatives were also tested for their nematicidal activity and compound 4 displayed significant and selective

• human cancer cells and evaluated for their nematicidal activity. Results and Discussion Semisynthesis of massarilactone D derivatives The reaction of massarilactone D with methacryloyl chloride in triethylamine in the presence of catalytic amounts of 4-dimethylaminopyridine afforded compound 2 (11

• prostate cancer PC-3, epidermoid carcinoma A431, ovarian carcinoma SKOV-3, and breast cancer MCF-7 cell lines. Although the parent compound was not active as previously described [15][16], compounds 2 and 3 exhibited a significant cytotoxic activity against all the tested cells lines with IC50 values

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• isolation from cyanobacteria [2], their extraordinarily high cytotoxicity was apparent and attracted attention, not least because of their still high efficacy against multidrug-resistant (MDR) cells [3]. Cryptophycin-52, a synthetic development candidate by Eli Lilly based on the initially discovered

• amines still show nanomolar activity against the MDR cell line KB-V1 (Table 1) with resistance factors FR (being the ratio between IC50 (KB-V1) and IC50 (KB-3-1)) of 25 (1) and 34 (2), thus being comparably much more potent against KB-V1 cells than for example the unit D analogues (FR ≈ 103) [19

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• displacement parameter restraints. View of the packing of the unit cells of a) Me2B viewed normal to the c-axis and b) Me4B viewed normal to (110). Only the majority occupied moiety of the N–N bridge is shown in Me4B. UV–vis spectrum of Cl2B after irradiation in DCM. Proposed mechanism for the topochemical [2

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• vitro and in living cells using rationally designed electrophile-tethered derivatives of preQ1 (1) and its Watson–Crick diamino-faced counterpart DPQ1 (2, Scheme 1A). These ligands (compound classes 3 and 4, Scheme 1A) were tailored to target a conserved guanine nucleobase within a natural preQ1-binding

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• achieve better stereocontrol and to facilitate the formation of synthetically challenging glycosidic linkages. Keywords: chemical O-glycosylation; neighbouring group participation; remote group participation; solvent effect; stereocontrol; Introduction Cell surface glycans in living cells have

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• MTT assay was used to determine the anticancer activity of compound 7a against these cultures (Figure 6). The viability test is an important method to determine which new compounds are able to target cancer cells. The results of this test (IC50 value ± 95% confidence interval) allow us to evaluate the

• cell culture, at which the number of live cells was reduced by 50%, was 0.172 ± 0.029 μM. For the H1299 culture, this value was 2.18 ± 0.7 μM. In comparison, the IC50 value of the standard anticancer drug cisplatin at 24 hour incubation is 137 ± 12 μM for the A431 culture [31] and 34.9 μM for the H1299

• , CN) (Aldrich) were used to prepare the solutions. Spectral fluorescent experiments were performed using quartz cells (lcuvette 1.0 cm, volume V 2 mL). Stock solutions of compounds 7 or 8 (c 5.0 × 10−5 mol L−1) and tetrabutylammonium salts (c 1.0 × 10−4 mol L−1) in acetonitrile were used. The

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• prepared in DMSO and cancer cells were treated with 10 μM doses of compounds using the apoptosis inducing standard mensacarcin (10 μM) as a positive control [56]. Only compound 7l decreased cell viability to 63%, while the rest of the compounds showed very low to no significant decrease in cell viability

• mammalian cells in vitro. Results of the microbroth single-dose assays revealed that two of the synthesized compounds have selective antibiotic activity against S. aureus. Subsequently, MIC90 values were calculated by performing microbroth dilution assays using serial dilutions of these two compounds

• against three different strains of S. aureus. Compound 7b has a MIC90 of 16 μg/mL, and 7h exhibited a MIC90 of 8 μg/mL against susceptible, methicillin-resistant, and multidrug-resistant S. aureus. So, it was observed that both of these compounds destroyed designated bacterial cells in a competitive

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• activity, inhibiting approximately 70% of Staphylococcus aureus biofilms at concentrations as low as 3.9 µg/mL. Keywords: antibiofilm; antiproliferative; beauvericin; insect pathogen; Samsoniella; Introduction A microbial biofilm represents an assemblage of planktonic cells to overcome hostile living

• . aureus biofilms with farinosones D (1) and A (2). This distinction is pivotal in the evaluation of compounds for their antibiofilm efficacy, considering the potential scenario wherein a compound may affect the growth dynamics of cells without substantially disrupting the biofilm architecture or

• dispersing the encapsulated cells [16]. The results (Figure 6) yielded striking significance, revealing that the biomass remained metabolically inactive in biofilms treated with 1 and 2 low to concentrations of 3.9 and 1.9 µg/mL, respectively. It is worth noting here that both compounds followed a similar

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• -established for their use in organic photovoltaic cells and as efficient photosensitizers for singlet oxygen generation. In 2022, Goddard et al. have reported the groundbreaking use of squaraine derivatives as novel organic NIR photocatalysts for various chemical transformations, marking the first application

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• improving the stability of inverted perovskite solar cells [23]. On the other hand, benzo[rst]pentaphene-5,8-dione (BPP-dione) is known as an oxidation product of BPP [24][25], but to the best of our knowledge, the detailed optical properties of this BPP derivative have not been previously described in the

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• enantiopurity at 130 °C for 48 h in toluene. Investigating the biological activity for a number of compounds, good cytotoxicity was reported for five kinds of cancer cells. The mechanistic study suggests that the indole ring of the substrate is having a crucial role in the reaction mechanism because replacing

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• , which results in more rigid domains. The anomalous shapes observed, with bending starting from seemingly random positions, support this hypothesis (Supporting Information File 1, Figure S36). These irregular shapes are reminiscent of some anomalous shapes observed in red blood cells [25]. It was also

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• fluorescent chemosensors and probes [4][5][6], as well as materials for applications in organic light-emitting diodes (OLEDs) [7][8][9], organic field-effect transistors (OFETs) [10], and perovskite solar cells [11]. In this respect, replacing either one or more of the carbons or rings of a fluoranthene with

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• cytotoxicity against L1210 murine leukemia cells and KB epidermoid carcinoma cells. Keywords: ceratinadin; cytotoxicity; marine sponge; psammaplysin; Pseudoceratina sp.; Introduction Marine sponges are widely recognized as a rich source of unique bioactive natural products. For instance, marine sponges

• ceratinadin G (1) was evaluated against L1210 murine leukemia cells and KB epidermoid carcinoma cells. Ceratinadin G (1) showed moderate cytotoxic activity against L1210 cells (IC50 = 4.7 μM) and KB cells (IC50 = 15.1 μM). Conclusion Ceratinadin G (1) is the first psammaplysin derivative identified to contain

• -1500 spectropolarimeter. 1H and 13C NMR spectra were acquired on a Bruker Avance II 600 MHz NMR spectrometer equipped with a cryoplatform, using 3.0 mm micro cells (Shigemi Co., Ltd.) for CD3OD. The 1H NMR chemical shift of residual CD2HOD in CD3OD at 3.35 ppm and the 13C NMR chemical shift of CD3OD at

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• cultures at 37 °C in LB medium were washed once with sterile saline 0.9% (w/v) and adjusted to an OD600 of 0.05. Then, 1% inoculum was transferred into fresh LB medium. Following the incubation at 37 °C, 200 rpm for 5–6 h to reach the mid-log phase, the cells were washed once with sterile saline 0.9% (w/v