Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• others (11–19) (see Figure 1), which may serve as virulence factors [8][9][10][11][12][13]. Most significantly, some of these indoles have been shown to be potent aryl hydrocarbon receptor (AHR) ligands [8][9][14][15], which can lead to induction of melanocyte apoptosis and inhibition of neutrophil

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• from the extracellular matrix (ECM) via inhibition of heparanase [19][20][21][22]. PI-88 is a complex mixture of monophosphorylated, highly sulfated mannose glycans derived from the extracellular phosphomannan of Pichia holstii NRRL Y-2448 yeast [23][24][25], which had progressed to phase III clinical

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

• tetrazolium structure in the MTT dye results in the formation of a coloured formazan that can be detected by spectrophotometry. Cytotoxic properties of the studied compounds were assessed on non-cancer as well as cancer cell lines. Cytotoxicity was established by measurement of 50% inhibition of cell growth

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

• activity than cotylenin A in cell growth inhibition assays and less toxicity in single-agent treatments [27][28]. Recently, Jiang and Renata described a chemoenzymatic approach that combines the skeletal construction by chemical methods and enzymatic C–H oxidations [29]. The synthesis employs a catalytic

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• infants and it has successfully completed a phase III clinical trial [17][18]. Finally, sulphonamide 4 is a lead compound for the treatment of osteoarthritis via MMP-13 (matrix metalloproteinase 13) inhibition which exhibited an excellent selectivity profile and complete inhibition of collagenolysis in

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• -3-phenylpropanenitrile (16ha), were successfully employed to construct the target polycycles. To verify the reaction mechanism, a series of control experiments were conducted. The complete inhibition of the reaction by radical scavengers such as TEMPO, BHT, and hydroquinone suggested a radical

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• -inflammatory [21][22] as well as enzyme inhibition activities [23][24][25][26]. Traditionally, β-ketophosphonates were prepared via Arbuzov reaction [27], acylation of alkylphosphonates [28], and hydration of alkynylphosphonates [29][30][31]. However, these methods have several drawbacks, including low atom

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

• not reach 100% growth inhibition at the assay top dose (80 µM), against Pf 3D7. Thus, determination of accurate IC50 values was not possible. The mean IC50 values (duplicate, n = 1) for compounds 10–14 against Pf 3D7 were calculated and are shown in Table 1. The antimalarial activity of 10–14 was

• limited activity against Pf 3D7 resulted in low selectivity indices, as indicated in Table 1. Compounds 3 and 13–15 demonstrated some inhibition of HEK293 at the highest concentrated tested, but did not display sigmoidal dose-dependent kinetics, thus accurate IC50 values were unable to be determined

• . Meaningful selectivity indices for these compounds could, therefore, likewise not be calculated. Hence, the mean % growth inhibition (duplicate, n = 1) at the top concentration is indicated in Table 1. Conclusion A modified approach for amine substitution of 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• (TXA2) synthetase inhibition [10], antinociceptive [11], histone deacetylase inhibition [12], α-glucosidase inhibition [13] , tyrosinase inhibition [14], allelochemical [15], anticonvulsant [16], antioxidant [17], antiplatelet aggregation [18], anti-inflammatory [19], and UV absorption [20]. Cinnamic

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

• ) production, with an IC50 value of 43.69 ± 5.26 µM. The presence of an electron-withdrawing group (-NO2 group) on the benzene ring at the 1-position of the pyrrolidine-2,3-dione subunit in compound 5e may be responsible for the observed high inhibition activity due to the enhancement and optimization of

• eliminate invading bacteria via the inhibition of metabolic enzymes and DNA destruction. However, overexpression of iNOS results in the overproduction of NO which is associated with septic shock and tissue damage [6]. Therefore, inhibition of iNOS could be considered a potential therapeutic strategy for

• drug dexamethasone (IC50 = 13.25 ± 1.39 µM). At a concentration of 100 µM, the NO inhibition of pyrrolidine-2,3-dione derivatives 5a, 5b, and 5e was 53.65%, 50.22%, and 63.65%, respectively, as compared to 85.04% of dexamethasone. It is clear that the presence of a nitro group or halogen atom on the

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

• the structural determinants of the recognition process is a prerequisite for understanding and manipulating carbohydrate–protein interactions, such as in the inhibition of carbohydrate-specific bacterial adhesion. For receptor binding, glycoligands have to be properly oriented in three-dimensional

• –inhibition assay. The measured results were systematically contextualized employing new reference compounds such as the respective homobivalent Man/Man glycocluster. An in-depth study comprising the analysis of the photochromic properties and the potential as inhibitors of bacterial adhesion of the synthetic

• of the various isomers at 37 °C are long enough to persist during the time a bioassay takes. In the PSS of the EE, EZ, and ZZ states, the respective isomers clearly predominate the mixtures and hence, testing the various isomeric states in bacterial inhibition–adhesion assays can lead to

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

• [14]. Massarilactones A and B were earlier shown to exhibit antimicrobial activity against Bacillus subtilis (ATCC 6051) and Staphylococcus aureus (ATCC 29213), affording zones of inhibition varying from 12 to 19 mm at 200 μg/disk [8], while massarilactone H displayed moderate cytotoxicity against

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• phenyl- or trityl-substituted 7c and 7d yielded products with decreased enantioselectivities, likely due to the inhibition of the interaction between the imines and the chiral catalyst by hydrogen and/or halogen bonding. From these observations, the substituent on the 1-position strongly affected the

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• cyclodextrin) can promote enantioselectivity [76], although turnover from augmented macrocycles is not always achieved [26]. The affinity of generic hydrophobic pockets for a hydrophobic product often leads to product inhibition, since binding a single large product is entropically favored over binding two

• hydrophobic catalysis as for the macrocycles discussed in the previous section [115], and so remain prone to product inhibition [113], though not exclusively [120]. Size- and regioselectivity are possible [121]. As with the two identical halves of a tennis ball/softball, it is harder to conceive unsymmetric

• concentration. As for the macrocycles discussed above, dual confinement/encapsulation [36] and the hydrophobic effect dominate the origin of catalytic rate enhancements [158][159]. To avoid product inhibition, model reactions that increase molecularity (A → B + C) or that generate weakly interacting or less

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

• decrease to normal values of 1800–2000 cm−1, indicating a complete inhibition of the ESIPT process. These spectral transformations are usually caused by the formation of a strong N–H(O–H)···CN− (F−) hydrogen bond up to deprotonation [28]. Using the principle of “relay recognition” [29], we investigated 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

• cell line HCT-116 (ATCC CCL-247) revealed that only compound 7l inhibited cell viability, while the rest of the compounds including 7b and 7h showed no significant decrease in mammalian cell viability. Results of human carbonic anhydrase (hCA) inhibition assays discovered that monoalkylated derivatives

• have low to negligible inhibition potential but dialkylated ones have no inhibition potential at all for directed CAs (I, II, IX, and XII). From the low inhibiting compounds, 7b showed the highest inhibition potential with a minimum Ki value of 72.9 μM. In light of the above findings, these newly

• -benzothiazine derivatives into a carbonic anhydrase inhibition assessment test. The design of the present research work is emphasized by all mentioned pharmaceutical contributions of benzothiazines and adjoining scaffolds. After synthesis following characterization, these new pyrazolobenzothiazine scaffolds

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

• screening assays were conducted to explore their antibiofilm properties. According to the crystal violet (CV) assay, both compounds exhibited significant activity in the S. aureus biofilm inhibition assay. Farinosone A (2) (Figure 5A) displayed activity at a concentration as low as 3.9 µg/mL, resulting in

• approximately 68% inhibition of biofilm formation. Similarly, farinosone D (1) demonstrated activity up to a concentration of 15.62 µg/mL, achieving a comparable inhibitory effect of approximately 74% at this dilution. In addition, only farinosone A (2) (Figure 5B) demonstrated moderate activity in the

• activity trend, reflecting the results from CV biofilm inhibition assay, where compound 2 was found to be more effective than compound 1. The genetic and molecular basis of biofilm formation in staphylococci are complex. This process involves at least two key properties: planktonic cell adherence to

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• whether the reaction proceeded through a free radical mechanism, different free radical inhibitors were added to the reaction (reaction 7, Scheme 5). The addition of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) resulted in complete inhibition of the reaction, while BHT (2,6-di-tert-butyl-4-methylphenol

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• inhibition of the reaction in the presence of TEMPO confirmed this hypothesis. The copper catalyst assisted in the addition step of the alkylsulfonyl radical X to the alkyne. The presence of 2-iodopropane as additive improved the yields. The role was unclear, but it might facilitate the conversion of the

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

• data analyses. All compounds were assessed for their inhibition on planktonic growth of P. aeruginosa PAO1 in addition to their ability to inhibit the formation of biofilms. None of the tested natural products inhibited planktonic growth or biofilm formation of PAO1 when screened at 50 µM

• , aplysterol (8) [13]. Our biological assessment of compounds 4–8 showed no inhibition of planktonic growth or biofilm formation for P. aeruginosa when screened at 50 µM. Previously reported antibacterial assessment of ianthelliformisamines A–C (1–3) and their synthetic analogues has generated structure

• . aeruginosa, including biofilm inhibition. Furthermore, this is the first report of any biological assessment of aplysterol (8) as a pure compound, since prior studies have only tested a mixture of 8 with 24,28-didehydroaplysterol, where it was found to inhibit DNA topoisomerase II-α (MIC = 50 µM) [22

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• paralysis rate of worms (Figure 4). Specifically, they exhibited a percentage of paralysis inhibition of 67%, 47%, 57%, 42%, 45%, and 64%, respectively, which indicates their potential in inhibiting β-amyloid toxicity in AD. These compounds were selected to assess their potential as acetylcholinesterase

• inhibitors, and their effects were investigated using the Amplex-Red® kit in C. elegans. Individuals exposed to compounds 2a, 2b, 2c, 2d, 2e, and 2f at a concentration of 1 mM were analyzed for AChE activity in their extracts. The results revealed significant inhibition of AChE levels, with compound 2e

• carboxylic building block. The obtained molecules were evaluated for their ability to inhibit β-amyloid aggregation by the interaction with two β‐amyloid peptides, Aβ1‐42 and AβpE3‐42. The aggregation inhibition experiment, which measures the decrease of fluorescence, was carried out with the thioflavin T

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• 4 [9][10] (Figure 1). Halogenated cyclised structures have also been found to exhibit medicinal and pharmaceutical properties, including antibacterial [11], antibiotic [12], and enzyme inhibition [13] among others. The general mechanism for the HVI-mediated halocyclisation of alkenes proceeds

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• cytotoxic compounds. For example, a cytotoxic effect was found in CAL 27 cells, presumably through a mechanism of TNF-α inhibition in vitro, which could be related to the anti-inflammatory effect identified in several studies of NSAIDs that inhibit cancer cell viability in vitro [37][38]. In another study

• with greater efficacy and selectivity against targets related to BC. Thus, the 1,5-disubstituted tetrazole-indole hybrids, presented different effects on cell proliferation inhibition in MCF-7 cells (Figure 1) that could be attributable to the molecular background of cells [46][47][48][49]. The

• compounds that elicited proliferation inhibition are ordered below from the highest to lowest effect on MCF-7 cell line: 18d, 18j, 18h, 18i, 18b, 18f, 18a, 18g, 18c, and 18e. Compounds 18c, and 18e did not affect MCF-7 cell proliferation inhibition. Regarding the structure–activity relationship, the

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• of action (MOA) (e.g., membrane lysis and depolarization) [30][34] and specific MOA (e.g., dysregulation of ClpP protease [33], inhibition of topoisomerase I/II [36][68], blocking lipid II transport by flippase [29], sequestration of cell wall biosynthetic intermediate C55-(di)phosphate, etc.) [35

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• presence of the oxime group (Scheme 21). In fact, it represents one of the most active non-glycosylated indirubin derivatives against cancer [11][28]. It has been reported that the free NH function of the indirubin is crucial for CDK inhibition. The reaction of isatin with thiaindan-3-one has been reported

• cytotoxic activity against melanoma and squamous cell carcinoma cells, lung cancer and glioblastoma cells [30]. It was shown in a WST-1 assay that these compounds exhibit a concentration-dependent inhibition of the metabolic activity of A375 and A431 cells, while the non-glycosylated derivative 34 proved to

• inhibition of colony formation were observed. Likewise, a concentration-dependent decrease of both the basal and ATP-linked oxygen consumption rate and of the capacity of oxidative respiration were observed at the mitochondrial level in the presence of compound β-33b. In addition, the morphology of the