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

• distal axial chiralities are widely applied in chiral ligands, natural products, and anticancer agents, with their unique spatial configurations endowing them with distinctive functions and values. Although significant progress has been made in the asymmetric synthesis of distal biaxial chirality

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

• and stabilizes a catalytically inactive form of the enzyme [11][12]. The BPTES scaffold has undergone significant medicinal chemistry development resulting in CB-839/telaglenastat, which is being evaluated in clinical trials in combination with other anticancer agents [13]. Compound 968 is a third

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

• , researchers have increasingly focused on developing novel organoselenium compounds as potential chemopreventive and anticancer agents [22][23][24][25][26]. Among these, the structures of a few representative examples are illustrated in Figure 1. Notably, the second-generation organoselenium compound

• comparable to or lower than those of the naphthalimide-based anticancer agents. These results indicate that the synthesised naphthalimide-organylselanyl conjugates 7 and 8 possess considerable anticancer activity against the MDA-MB-231 breast cancer cell line. Molecular docking study Following the in vitro

• insight into the design of new naphthalimide selenium-based lead molecules as promising candidates for potent chemotherapeutic anticancer agents. Further studies are underway to probe the extent of specificity of these compounds towards the EGFR receptor. Experimental General procedure All syntheses were

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

• ]pyrimidines and a series of 7-N-(1,4-diazepane)- and 7-N-piperazine-substituted 2,5-diaryl[1,3]oxazolo[4,5-d]pyrimidines were highly effective anticancer agents, as proven in a five-dose assay in NCI60 cancer cell line screen [11][12]. The most active derivatives of both series displayed high total

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

• sciences [13][14][15][16][17]. Their synthetic versatility, ease of functionalization, conformational rigidity or flexibility, steric bulk, and low cost make them highly attractive in the development of novel, non-conventional anticancer agents with a great potential for overcoming the toxicity of cancer

• responsiveness to conventional chemotherapy. To the best of our knowledge, calixarene derivatives have not been previously tested as anticancer agents against human renal carcinoma cells. Compound 3 suppressed the proliferation of the renal cancer cells (Figure 3) with a calculated 50% inhibitory concentration

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

• case of MCF7. Additionally, linear sweep voltammetry (LSV) studies on human serum albumin (HSA) were conducted to investigate their alkylating properties. The electrochemical results suggest that these compounds effectively modify albumin, highlighting their potential as reactive anticancer agents

• , indicating a trend toward moderate preferential cytotoxicity. These findings suggest that the glycidyl phosphorus esters, particularly compound 2, may serve as promising lead structures for further exploration as anticancer agents. A key innovation in this work was the application of linear sweep voltammetry

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• biomedical applications including as a solubilizing excipient for anticancer agents and as an in vivo sequestrant to reverse the biological activity of neuromuscular blocking agents, anesthetics, and drugs of abuse (e.g., methamphetamine and fentanyl) [54][55][56][57][58][59][60]. As a result of their

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

• representative studies include antibacterial, anti-inflammatory, antioxidant, selective inhibitor of COX-2 [34], and anti-HIV activity [35]. In this context, even though indole is considered a privileged scaffold present in some anticancer agents [36], a few examples of methanesulfonylindoles are studied as

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• , we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based α-acetamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell

• isatin-based Ugi reaction [16][20][21][22][23] and the potential of the bis-amide-oxindole type derivatives as anticancer agents, a second family was synthesized, and screened for their anticancer activities (Scheme 1B). Results and Discussion Synthesis Underlining sustainability and economically favored

• and lead-discovery are in progress and will be reported shortly. (A) Accessing libraries of oxindole hybrids using commercially available isatin as starting material and (B) most potent oxindole derivatives as BuChE inhibitors and anticancer agents, by Marques et al. [10][11][12][13][14][15][16

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• function in an organism, but the activities can also be detrimental. CDA is highly active in the liver and spleen, which results in deamination and consequent deactivation of several chemotherapeutic agents, including the anticancer agents cytarabine, gemcitabine and 5-aza-2'-deoxycytidine (decitabine) [2

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• ; Introduction Nonribosomal peptides (NRPs) exhibit various biological activities and have been used as therapeutic agents, such as antibiotics, anticancer agents, and immunosuppressants [1]. Additionally, NRPs function as virulence factors, such as siderophores and genotoxins [2]. Therefore, inhibiting their

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• -inflammatory, and even anticancer agents. Traditionally, the synthesis of BIMs has been achieved upon the acidic condensation of an aldehyde with indole, utilizing a variety of protic or Lewis acids. However, due to the increased environmental awareness of our society, the focus has shifted towards the

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• compounds, which have been employed in biomedical imaging and as potential DNA-targeting anticancer agents [14][15][16][17]. More recently, a benzoquinolizinium-based fluorescent dye was reported to be used as imaging agent for inflammation and for the evaluation of the physiological response to anti

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• , F, H, K, L, O, S, V, W, and X) [1]. Cathepsin C is considered a good target for designing new anticancer agents with broad substrate specificity [2]. Cathepsin C, which affects the processing of keratin, is of great importance in maintaining the structural organization of the epidermis, primarily

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• , since Pettit and co-workers, in a program from U.S. National Cancer Institute for the discovery of new anticancer agents, initially showed that combretastatins D-1 (1) and D-2 (2) isolated from the bark of the Combretum caffrum tree inhibited the growth of the murine lymphocytic leukemia cell line P388

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• larger cavity as compared to TBTQ-C6 due to the introduction of triazole rings. Two anticancer drug molecules, dimethyl viologen (MV) with a smaller size and DOX with a larger size, were selected as model anticancer agents for encapsulation by TBTQ-CB6 to form the host–guest complexes of TBTQ-CB6MV and

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• anticancer agents [21][22][23]. Previous reports of the synthesis of 1,3,4-oxadiazoles in continuous flow focused on the reaction between tetrazoles and carboxylic acids (Huisgen synthesis) [24][25]. Continuous flow technology has also been exploited for the further functionalisation of 1,3,4-oxadiazoles [26

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• -anilinoquinazoline; anticancer agents; N-arylation; 4-chloroquinazoline; microwave irradiation; Introduction N-Heterocyclic compounds are commonly present in pharmaceuticals, bioactive natural products, agrochemicals, and synthetic drugs [1][2]. Quinazoline, a benzo-fused N-heterocyclic framework (benzo-1,3-diazine

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• single-photon counting (TCSPC) experiments. The average fluorescence lifetime of compound 3ac was found to be 8.35 ns and 4.73 ns in DMSO and DCM, respectively (Table 2, Figure 4). Biological evaluation of γ-carbolines as anticancer agents A panel of carboline derivatives 3ac, 3bc, 3ca, and 3ga, along

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -alkylated pyridones are valuable scaffolds offering biological activity such as immunomodulators, memory-enhancers and anticancer agents [109][110]. A direct approach to achieve N-alkylated pyridones are less explored and those available present limitations such as poor selectivity and yields, expensive

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• coordination compounds with Cu(II) ions. The results of biological tests showed that the compounds containing an amino- or polyamino-substituent at the 4-position of the phthalazinone moiety could have potential applications as new anticancer agents. Structure of biologically active phthalazine derivatives

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• , such as monitoring of specific biological activities and as antimalarial and anticancer agents [5][6]. However, electroactive properties of derivatives of this acceptor have been scarcely reported. Quinazoline-based compounds were used as hosts for red phosphorescent OLEDs with an external quantum

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• . Securinega alkaloids The total synthesis of the Securinega alkaloids, (−)-flueggine A (18) and (+)-virosaine B (19), which are potent anticancer agents, was proposed by Wei et al. [90] via a relay ring-closing metathesis (RRCM) associated with a 1,3-dipolar cycloaddition. The enyne precursors bearing a