Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• cancer cells from moving. In this study, a unique plant-derived lignan‑based library was screened against glioblastoma (brain cancer) cell lines to evaluate anti-invasive and cytotoxicity effects. Results and Discussion The air-dried and ground seeds of E. maculata were sequentially extracted with CH2Cl2

• (MIC = 25 µM), and Malassezia furfur (MIC = 12.5 µM) [20]; antioxidant activity with the inhibition of CuSO4-induced peroxidation of low-density lipoprotein in a concentration-dependent manner from 0.1−10 µM [21], and anti-invasiveness activity on HT115 human colon cancer cells at a concentration

• vitro cytotoxicity and anti-invasive properties using two glioblastoma cancer cell lines [23][24]. During our semisynthetic studies, several reactions including methylations, halogenations, and acylations were performed, leading to the generation of five analogues in varying yield (10−81%) and high

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• Centre supplementary scholarship. YHL acknowledges funding from the National Health and Medical Research Foundation Investigator grant (2041692), Synergy grant (2045600), and funding from the Cancer Institute of New South Wales Career Development Fellowship (2024/CDF1222).

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• , ARV-766, and CC-94676, are currently being evaluated in patients with prostate cancer, demonstrating that the event-driven pharmacology of PROTACs translates into durable target knockdown in humans [30][31][32]. Beyond the AR, the clinical landscape is expanding to include targets discussed

• often exist in cancer and nervous system diseases [47]. Palbociclib was the first small-molecule inhibitor approved by the FDA in 2015 to target CDK4/6 in the CDK family [48]. Soon after, ribociclib and abemaciclib, small-molecule inhibitors targeting CDK4/6, were also approved by the FDA for breast

• cancer treatment [49][50]. However, due to the high homology of the CDK family (for example, the homology of CDK4/6 is 71%, the homology of CDK2/3 is 76% [51], the homology of CDK8/19 is 97%) [52], small-molecule inhibitors may often inhibit several CDK members, thus, to a certain degree, cause off

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• , Faculty of Science, Palacky University, Tr. 17. Listopadu 12, Olomouc, 77900, Czech Republic Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1GA, United Kingdom Hit Discovery, Discovery Sciences, R&D, AstraZeneca, Cambridge, CB2 0AA, United Kingdom Cancer Research UK

• survival across several cancer types, and its downregulation impairs viability in models of glioblastoma, medulloblastoma, cholangiocarcinoma, breast and renal cancers [4]. These features have established CK2 as a compelling therapeutic target. In 2016, structural studies revealed a cryptic αD pocket

• for their ability to induce degradation of CK2α and CK2α′ in cell-based assays. Western blot profiling across six colorectal cancer cell lines revealed heterogeneous expression of both CK2 isoforms. HCT116 cells exhibited robust expression of CK2α and CK2α′, with CK2α predominating, and were therefore

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• rearrangements or fusions involving FGFR2 can create novel chimeric proteins with enhanced or aberrant signaling capabilities, further driving cells towards a malignant phenotype [13][15]. Notably, FGFR2 amplification and fusions are frequently detected in patients with advanced gastric cancer and

• functions and overcome a series of critical issues in cancer treatment. The numerous advantages of PROTAC technology in targeted therapy have prompted us to conduct further research into FGFR2 degraders. In this work, a series of degraders conjugating erdafitinib with a CRBN binder was synthesized and

• screened, leading to the identification of LC-JD-6, a potent and FGFR2-selective degrader. This study establishes a fundamental framework for the rational design of therapeutic modalities targeting FGFR2 degradation, offering novel insights into protein homeostasis-based cancer intervention. Results and

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