Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• , acetophenones and quinolone alkaloids. Moreover, several Melicope species are used in traditional and modern medicine. Some of the constituents possess antibacterial, antidiabetic, cytotoxic and antiproliferative activities in human cancer lines [1]. Five years ago, we described new acetophenones and chromenes

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• , Halaven) due to its unique mechanism of action as a microtubule dynamics inhibitor. It is primarily used in the treatment of metastatic breast cancer and liposarcoma, offering a new therapeutic option for patients with advanced disease. To meet the increasing clinical demand, the research on new synthetic

• eribulin are summarized. Keywords: breast cancer; drug manufacturing; eribulin; Halaven; total synthesis; Introduction Eribulin (1) is a truncated derivative of halichondrin B (2), a complex natural product originally isolated from the marine sponge Halichondria okadai (Figure 1) [1][2][3][4][5]. Already

• within their isolation study on halichondrin B, in 1986, Hirata and Uemura showed its promising activity against murine cancer cells [6], which led to a great interest in the pharmaceutical society [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Only 6 years later, Kishi and co-workers first

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• (Scheme 11) [52]. A preliminary biological evaluation revealed inhibitory activity of selected products against MV4-11 cancer cells, highlighting their potential in pharmaceutical research. At the same time, efficient synthetic routes to uracils bearing a single C–N axis were also achieved in yields

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

• Lindsey A. Albertelli Sainabou Jallow Chun Li Scott M. Ulrich Department of Chemistry, Ithaca College, Ithaca, NY 14850, USA 10.3762/bjoc.22.33 Abstract Many cancer cells require extracellular glutamine to meet the energetic, biosynthetic, and redox demands of the proliferative state

• . Glutaminases catalyze the hydrolysis of glutamine to glutamate, which supports the biosynthesis of amino acids, lipids, and glutathione and can also be oxidatively deaminated to α-ketoglutarate and enter the citric acid cycle. The “glutamine addiction” of cancer cells has made glutaminase an attractive

• anticancer drug target. Compound 968 is a glutaminase inhibitor that is widely used to probe cancer cells’ dependence on glutaminase activity. Here, we show by NMR spectroscopy and X-ray crystallography that the reported benzo[c]phenanthridine structure of compound 968 is incorrect; its true structure is the

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• , metabolic diseases, vascular diseases, cancer, neurologic diseases and so on. Notably, taxifolin has been approved as a novel dietary additive by the U.S. Food and Drug Administration (FDA) and is widely used as a food ingredient in various markets. It is to be expected that taxifolin undergoes

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

• structurally characterised by single-crystal X-ray diffraction analysis. The anticancer potential of the NAP-SePh and NAP-Se(n-Oct) was evaluated using an in vitro cell viability assay with MDA-MB-231 triple-negative breast cancer (TNBC) cells. The IC₅₀ values for compounds NAP-SePh and NAP-Se(n-Oct) were

• epidermal growth factor receptor (EGFR) in which erlotinib, a well-known anticancer drug, binds. Keywords: cell line study; density functional theory; MDA-MB-231; molecular docking; organoselanyl conjugates; Introduction Cancer remains one of the most common and life-threatening diseases globally, posing

• a serious challenge to health and survival [1][2]. Among its various forms, breast cancer is a major concern, particularly for women, as it accounts for a significant proportion of cancer-related morbidity and mortality worldwide [3]. Breast cancer affects one in ten cancer patients worldwide [4

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

• liquid chromatography–mass spectrometry. Their anticancer activity was assessed against human cancer cell as well as non-cancer cell lines. Three compounds, 1, 3, and 9, were the most cytotoxic to HeLa cells (IC50 = 6.13 ± 1.95, 13.99 ± 1.80 and 49.92 ± 3.98 μM, respectively). However, only compounds 1

• -mimicking scaffolds are a proven strategy in the design of anticancer drugs. Many cancer-related proteins (e.g., kinases, ATPases, DNA/RNA polymerases) have binding pockets designed for purine nucleotides (ATP, GTP). Oxazolopyrimidines can compete with purines or their analogues, inhibiting enzymatic

• activity. They combine purine-like recognition features with the synthetic flexibility of heterocycles, offering a platform for selective targeting of tumor-related enzymes and receptors. Tumor cells overexpress kinases, DNA/RNA polymerases, and metabolic enzymes that bind purine nucleotides. Cancer cell

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

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

• X-ray diffraction analysis (XRD) for two adducts, followed by Hirshfeld surface analysis. The antiproliferative effect of the synthesized compounds against cancer cell lines was assessed. Keywords: alloxan; antiproliferative activity; azomethine ylides; 1,3-dipolar cycloaddition; maleimides

• [a]pyrolizines as well as spiroazabicyclo[3.1.0]hexanes are readily available from cyclopropenes and azomethine ylides [47][48][49] and some adducts inhibited cancer cell growth in vitro [50][51]. The first reported synthesis of spirobarbiturates employing azomethine ylides (generated in situ from

• potential in the brain with regard to bioavailability in the CNS. Antiproliferative activity study. Cancer cells are favorable in vitro models that are widely used in cancer research and drug discovery. In this study, the MTS assay was applied to evaluate the antiproliferative activity of the synthesized

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• spectrum. Previously reported related meroterpenoids, such as thallusin and saccharoquinoline, exhibited no antibacterial biological activities – thallusin acts as an inducer of morphogenesis in some marine algae [7], whereas saccharoquinoline exhibits cytotoxicity towards the HCT-116 cancer cell line

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• biologically active properties. Thus, barbamide exhibits molluscicidal activity [7], and sintokamide A is active against prostate cancer [8] (Figure 1). As derivatives of strained and unique structure and properties [9][10] cyclopropanes are of interest for entering into various transformations along the path

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

• , and low toxicity make calixarene derivatives valuable drug candidates against cancer. The aim of the present study was the synthesis and characterization of a calix[4]arene derivative in which known anticancer isothiouronium groups were clustered on a calix[4]arene scaffold bearing long C12 alkyl

• chains at the lower rim. The resulting amphiphilic calix[4]arene derivative 3 spontaneously self-assembled into nanoscale aggregates in aqueous medium, as demonstrated by dynamic light scattering analysis. The cytotoxicity of compound 3 towards cancer cells was assessed using human renal carcinoma cells

• (786-O cells) and compared with that in non-malignant fibroblast cells (SW1 cells). Compound 3 showed a significantly greater antiproliferative effect on cancer cells (IC50 37.4 µM) than on normal fibroblasts (517 µM). The importance of the isothiouronium moieties in the observed cytoxic effect was

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• bacteria or malignant cells like cancer) [5][6], or to influence membrane protein function and thereby control cellular behavior [7][8]. One promising approach is the development of light-activated molecules that can modulate membrane properties upon irradiation, enabling remote activation with high

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

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• influenza [7], while chlorinated analogues such as 3 have demonstrated activity against hepatitis C (Figure 1) [8]. Stereoselective methods to access halogenated γ-butyrolactones are therefore valuable, as they enable access to nucleoside analogues which have applications in treating cancer and certain

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

• VS-77 which has now a significant affinity toward CLK3 (IC50 = 0.3 μM). Thus, VS-77 appears as a new pan-inhibitor of the CLK family. Keywords: cancer; CLK3; kinases; molecular modelling; quinazolines; triazoles; Introduction Human protein kinases are a family comprising nearly 535

• ][12]. In particular, these CLKs are involved in the regulation of mRNAs splicing with important consequences especially in cancer [13]. There are four isoforms of CLKs (CLK1, CLK2, CLK3, and CLK4) whose structures have been clearly established and are available in PDB. Among the CLKs family, CLK3

• appears presently as the less studied, although it has been implicated in cancer as well as in other unrelated diseases like malaria [14][15]. Further, it has been proposed to play also a role in the formation of the central nervous system [16]. The lack of knowledge around CLK3 is likely due to the fact

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

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

• biological evaluation of novel indolo[1,2-c]quinazoline derivatives, with a particular focus on their antiproliferative potential against human cancer cells. We introduced structural modifications at positions 5, 6, and 12 of the indolo[1,2-c]quinazoline core to explore the structure–activity relationships

• evaluation. The antiproliferative activity of the novel indolo[1,2-c]quinazoline derivatives was evaluated against several human cancer cell lines, including colon carcinoma HCT116, lung adenocarcinoma A549, and chronic myeloid leukemia K562. To estimate selectivity for non-malignant cells human skin

• towards all tested cancer cell lines. However, no clear correlation between structure and activity was observed. For example, elongation of the alkyl substituents (N,N-diethylamino derivative 9b) led to a complete loss of antiproliferative activity, while its cyclic analog 9c showed the lowest IC50 value

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

• approved for treating several cancers, including gastrointestinal tumors and bladder cancer (Figure 1). Additionally, phosphoric triamides alkylating agents featuring aziridine rings are recognized for their role as nitrogen mustards in cancer therapy [24]. Although there are numerous examples in the

• . 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

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

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

• cyclodextrins in terms of controllable functionalization [61]. In clinical applications, particularly for anticancer drug conjugation, CAs demonstrate remarkable cancer cell selectivity, minimized off-target effects, enhanced delivery efficiency, and reduced systemic toxicity. Additionally, their synthetic

• [52]. The key design features are: 1) The mannose groups at the upper rim confer specific recognition ability for cancer cell surface receptors; 2) The hydrophobic core formed by the alkyl chains at the lower rim and the hydrogen-bonding network constructed by the thiourea unit can efficiently

• carrier has made significant progress in the field of hypoxia-targeted drug delivery. This section highlights several recent studies on stimulus-responsive drug release within hypoxic tumor environments. Among anti-cancer drugs, BE-43547A2 (BE) exhibits high cytotoxicity against hypoxic pancreatic cancer

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• polysaccharide (PS A1) (1), which has been shown by Andreana et al. to significantly activate the immune system and therefore recognized as a promising candidate for cancer immunotherapy [2][3][4][5]. This distinct structure is crucial for regulating the transportation of substances across cell membranes and

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• studied in hormone replacement therapy (HRT). However, HRT produced some risks of breast and uterine cancer. Consequently, scientists then concentrated their efforts on developing selective estrogen receptor modulators (SERMs) that interact with intracellular ERs in a tissue-specific manner to reduce the

• frontier for treating breast cancer, osteoporosis, cardiovascular disease, neuropathies, and other diseases. Merck scientists found that molecules with tetrahydrofluorenone (6/5/6 tricyclic motif) can act as SERMs. For example, molecules I and II (Scheme 1A) displayed low nanomolar affinity for ERβ and

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

• -hydantoin-1,2,4-oxadiazolines against the HCT116 human prostate cancer cell line, and compared it with that of compounds containing either spiro-hydantoins or spiro-oxadiazolines alone. Although there are many examples in the literature demonstrating the ability of nitrile oxides to react with various types

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

• 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

• 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