Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• confirm that the conjugation of CI-994 to the nanogold particle did not significantly affect HDAC inhibition. The HDAC1-LSD1-CoREST complex, incorporating a FLAG tag in CoREST, was expressed and purified from HEK293F cells as previously reported [10]. Fluorescent deacetylase assays were carried out using

• -complete inhibition of the HDAC activity in the CoREST complex, even at 0.54 μM. Surprisingly, Au–NH2 was found to reduce the HDAC activity of the CoREST complex by nearly 50%. One plausible explanation for this effect is a direct interaction between the gold nanoparticles and solvent-accessible cysteine

• complex and diminishing its deacetylase function. However, the maximal HDAC inhibition by Au–NH2 was considerably less compared to Au–(CI-994) and CI-994, suggesting Au–(CI-994), is inhibiting HDAC enzymatic activity by direct competition for the HDAC active site. We next determined the IC50 of Au–(CI-994

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• demands of the proliferative state creates an opportunity to selectively target cancer cells [1][7]. Chemical inhibition of GLS has emerged as an attractive anticancer strategy, and several classes of GLS inhibitors have been discovered [1][2]. DON is a diazo-containing electrophilic glutamine analog that

• glutaminase inhibition on several cancer cell lines (Figure 1) [15][16]. The anticancer effects of compound 968 have been tested in combination with other drugs such as paclitaxel [17], erlotinib [18], apigenin [19], metformin [20], and inhibitors of tissue transglutaminase [21]. Compound 968 was recently

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• enhancing lysosomal membrane permeability and aqueous solubility [42]. Interestingly, for the first time, N-(n-octyl) chain substitution has been shown to demonstrate remarkable anticancer activity, particularly through tyrosine kinase inhibition, without significant DNA intercalation [43]. Among these

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• carcinoma cells), and T98G (Human glioblastoma multiforme cells). Cytotoxicity was determined by measurement of 50% inhibition of cell growth by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The selectivity index (SI) was calculated for the investigated compounds. The

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• antiandrogen cancer treatment [8][9] (Figure 1). Moreover, aminosulfones remain a privileged scaffold in the ongoing development of new methods for the synthesis of pharmaceuticals [10][11][12], with multiple research compounds showing promising bioactivities such as MMP inhibition [13], antiinflammatory

• effects [14], сoagulation enzyme factor (FXa) inhibition [15] and antidepressant properties [16]. Considering the approaches to the synthesis of γ-aminosulfones, we focused our attention on the implementation of an aminoalkylation as a powerful and versatile tool for the synthesis of aliphatic amines [17

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• absorption (HIA), in vitro permeability to Caco-2 cells (Caco2), in vitro binding to plasma proteins (PPB), solubility, and inhibition of CYP2D6. The following were selected as descriptors of toxicity: carcinogenicity for rats and mice, mutagenicity according to the Ames test, and cardiotoxicity by

• inhibition of hERG in vitro. The results are shown in Supporting Information File 1, Table S5. As can be seen from the table, the obtained results suggest that the compounds have a good intestinal absorption and medium permeability. However they are expected to have low plasma protein binding and permeation

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• vivo using the diffusion-in-agar method [49] against Escherichia coli ΔtolC and E. coli lptD mutant strains. None of the compounds exhibited activity against the lptD mutant. Compound 12a showed the broadest growth inhibition zone, with compounds 9c and 13a also demonstrating significant effects

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• as a potent inhibitor of ornithine decarboxylase, the key enzyme that catalyzes the first step in polyamine biosynthesis [6]. This inhibition underlies both its therapeutic utility and its importance as a biochemical probe. From a structural standpoint, DFMO provides an intriguing case study for

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• ), Bipolaris sorokiniana (B.s., ascomycete causing root rot and spot blotch), and Sclerotinia sclerotiorum (S.s., ascomycete affecting sunflower, potato, and other cultures). The degree of mycelium growth inhibition on potato-sucrose agar amended with the studied compounds (30 mg/L) was used as the criterion

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• confirmed its mode of action by inhibition of the hedgehog signaling pathway, which plays a critical role in the differentiation and symmetry in the development of embryos [35]. We will have a further look into four different approaches to synthesize this natural product. The first synthesis was reported by

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• evaluation and structure–activity relationship studies. The systematic investigation of the their key biological activities, including estrogenic activity (assessed via breast cell proliferation assays), antitumor activity (evaluated through HeLa cell inhibition assays), and antibacterial activity (evaluated

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• mechanisms including elevation of reactive oxygen species (ROS) or interference with redox homeostasis, and inhibition of kinase or topoisomerase activities essential for cancer cell proliferation. The selective activity of thiouronium salts against cancer cells compared to non-malignant cells can be related

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• 2012, Lin and co-workers [69] isolated the membrane diterpenoid (−)-134 from the marine soft coral Sinularia pavida. The study showed that (−)-134 exhibits highly selective inhibition against the human promyelocytic leukemia cell line HL-60 with an IC50 of 2.7 μg/mL. Structurally, (−)-134 contains a

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• ). Dysifragilone A (34) displays stronger inhibition of NO production than hydrocortisone, with an IC50 of 6.6 μM. Dysideanone B (35) shows cytotoxicity against HeLa and HepG2 human cancer cell lines, with IC50 values of 7.1 and 9.4 μM, respectively. Septosone B (37), featuring an unusual spiro[4.5]decane scaffold

• , characterized by a [5,6]-bisbenzannulated spiroketal moiety as its central structural motif. This key feature is critical to its potent biological activities, including strong inhibition of human telomerase [52], as well as its established roles as an effective antibiotic and HIV-1 reverse transcriptase

• inhibition (>5.75 × 10−4 M) against Alternaria solani [55]. In 2023, Suzuki's group pioneered the enantioselective total syntheses of preussomerins 97–99 through their photoredox strategy [49]. This study addressed the key challenge of controlling spiroacetal stereoselectivity through a 1,6-HAT process – a

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• that no potent and selective inhibitor of this specific kinase has been reported, to the best of our knowledge. Among the Tchem kinase inhibitors [9], only four molecules demonstrated significant enzymatic inhibition of CLK3 (from 6.5 nM to 110 nM, Table 1, [10]): SM08502, T-025, T3, and CX-4945

• reagent the 3-(methoxycarbonyl)phenylboronic acid ester 11. All derivatives have spectral and analytical data in agreement with the proposed structures (see experimental section and Supporting Information File 1). Kinase inhibition studies Our molecules have been submitted first to a primary screening

• to observe a dose-dependent effect from 1 to 10 µM for these compounds (e.g., the same level of inhibition was observed when 12a was tested at 1 or 10 µM against CLK1). For the hit compounds that showed an inhibitory activity, we next determined their respective IC50 against the four mouse CLKs. The

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• Hamigera tarangaensis, and show cytotoxicity against various tumor cells. Notably, compound 11 exhibits 100% inhibition against herpes and polio viruses without significant host cell cytotoxicity [38]. Since their isolation, the synthesis of 11 and 12 have been reported by many groups [39][40][41][42][43

• -bromohamigeran B (12), respectively. Total synthesis of (+)-randainin D (+)-Randainin D (13) is a representative member of a class of structurally intriguing diterpenoids containing a trans-hydroazulenone core and a C9-butenolide moiety isolated from Callicarpa randaiensis [52]. It exhibits inhibition of

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• indolo[1,2-c]quinazoline derivatives was patented as anti-HCV compounds acting through selective inhibition of viral polymerase (Figure 1, top) [17]. Other notable bioactive indoloquinazoline compounds include the natural alkaloids tryptanthrin and hinckdentine A (Figure 1, bottom). Tryptanthrin (indolo

• [5,6,1-jk]carbazoles possessed exceptionally high in vitro and in vivo antitumor potencies though topoisomerase II inhibition (Figure 1, bottom) [20]. Taken together, an emerging evidence points to the remarkable pharmacological versatility of indolo[1,2-c]quinazoline derivatives, highlighting the need

• : indolo[1,2-c]quinazoline derivative 7c bearing a 4-aminobutyl substituent showed weaker DNA binding and cell growth inhibition. Moreover, the measured dissociation constants for the most active derivatives indicated a lack of significant binding to dupex DNA, suggesting that their cytotoxic effects on

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

• , 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

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