Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• ) from marine sponge associated fungus Aspergillus versicolour SCSIO XWS04 F52 [32]. They reported that both the two alkaloids showed cytotoxic activity against leukaemia K562 and colon cancer cells SW1116 with IC50 ranged from 7.5 to 12.5 μM, and significant protection against H1N1 virus-induced

• cytopathogenicity in MDCK cells with IC50 values of 15.5 and 24.5 μM, respectively. Attracted by both their structure and bioactivities, we anticipated their synthesis. The author determined the structure by means of spectroscopic (1H, 13C NMR, HSQC, HMBC, and 1H-1H COSY), and MS analysis, and claimed that “their

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• calculations, and chemical transformations. Biologically, these molecules exhibit antineuroinflammatory activity against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells. Structurally, these molecules generally have a tetracyclic backbone (A–D rings), among which AB rings form a bridged

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• pivotal position among renewable energy sources. To date, solar energy conversion and storage technologies have experienced considerable progress, including artificial photosynthesis [1], solar thermal collectors [2], photovoltaic cells [3], and solar thermal fuels [4][5]. Among these innovations, solar

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• , obtaining products with high purity and moderate to excellent yields. Their cytotoxic potential was evaluated using the MTT assay on human fibroblasts (HSF), prostate cancer (PC-3), and breast cancer (MCF7) cell lines, revealing moderate preferential cytotoxicity toward cancer cells, particularly in the

• , PC-3, and MCF7 cell lines, respectively. Similarly, diglycidyl methylphosphate (2) achieved 50% inhibition at concentrations of 398 ± 33 μM, 300 ± 21 μM, and 128 ± 10 μM. Triglycidyl phosphate (3) exhibited IC50 values of 254 ± 19 μM for HSF, 257 ± 20 μM for PC-3, and 182 ± 14 μM for MCF7 cells

• . Among the tested compounds, triglycidyl phosphate (3) demonstrated the highest overall cytotoxicity against HSF and PC-3 cell lines, while diglycidyl methylphosphate (2) showed the greatest potency toward MCF7 breast cancer cells. Although the IC50 values for compounds 1 and 2 were somewhat higher in

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• moderate yields and required geometrically complex divided cells. In 1989, a more efficient procedure was introduced by Torii et al. [43], who simplified the process by using PbBr2, TFA and THF, in a beaker-type undivided cell equipped with two platinum electrodes. This approach afforded vicinal diamines

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• π–π stacking interactions [86]. Their amphiphilic nature enables these systems to enter cells efficiently through endocytosis, providing a new drug delivery approach and holding great potential in precision medicine due to their programmable and stimulus-responsive features. Additionally, PAs can be

• example, the acidity of tumor and inflamed tissues is distinct from that of healthy tissues, offering a potential physiological trigger for pH-responsive drug delivery. Thus, drug release can be regulated by leveraging the variations in acidity between normal and diseased cells [100]. Developing

• down by the highly acidic environment of tumor cells, which acts as an exogenous or endogenous stimulus to enable the controlled release of the encapsulated drugs. These nanosystems are highly compatible with the body and comprise biocompatible, water-dispersible, and low-toxicity small molecules. 2.2

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• therapeutic efficacy (lower IC50 values) [18] but greater toxicity to healthy cells in comparison with spiro compounds [19]. Such hybrid-designed molecules may contain a third heterocycle as a linker, spiro-joined with one of the pharmacophore moieties. In this case, another pharmacophore fragment is included

• aromatic core hinders rotation around the C–N bond. Cytotoxicity The cytotoxic properties of hydantoin/1,2,4-oxadiazoline spiro-compounds were investigated using the MTT [42] assay on human colorectal carcinoma cell line HCT116. To evaluate the cytotoxicity of the compounds in vitro, cells were placed in

• 96-well culture plates at a concentration of 4–7 × 103 cells/mL and incubated at 37 °C for 24 hours. The cells were counted after treatment with trypan blue solution (0.4%) in a Goryaev chamber. Then, after incubation at 37 °C for 72 h, the cells were exposed to various concentrations of the studied

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• isomeric products was a feasible operation. Cytotoxicity of selected thioaminals 9 and dithioacetals 10 in cancer and non-cancer cells Cytotoxicity investigations represent a pivotal component in the realm of pharmaceutical development and contemporary medicine. In vitro assays constitute a rapid method

• by MTT assay and expressed as CC50 parameter (50% cytotoxic concentration) [32]. All results are gathered in Table 2. In general, the tested compounds did not demonstrate high levels of toxicity towards the investigated non-cancer cell lines. Among them, Vero cells showed the highest sensitivity

• insensitive to the investigated compounds (CC50 > 1000 µM for HepG2, A549 and CC50 > 300 µM for T98G), whereas HeLa cells demonstrated increased sensitivity. The most active compounds 9a, 9h and 10i, revealed their toxicity with CC50 < 10 µM (6.35 ± 1.75 µM; 2.11 ± 0.53 µM and 9.26 ± 3.14 µM, respectively

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• -inflammatory, antimicrobial, antiparasitic, and plant growth regulating activities. For instance, cotylenin A (1) and fusicoccin A (2) function as molecular glues to stabilize the interactions between 14-3-3 proteins and their binding partners in plant and animal cells [8][9][10][11][12]. It has been reported

• that cotylenin A and its aglycone, cotylenol (3), induce differentiation in murine and human myeloid leukemia cells [13]. Cotylenin A and fusicoccin A also act synergistically with interferon-α or rapamycin to induce apoptosis in cancer cell lines [14][15][16]. However, cotylenin A cannot be produced

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