Triazole-based hybrid molecules in anticancer drug discovery: structural classes and mechanistic insights, 2014–2025

• Meena Bhandari,
• Akshi Goyal and
• Deepak Yadav

Beilstein J. Org. Chem. 2026, 22, 1168–1195, doi:10.3762/bjoc.22.94

• antiproliferative action for MCF-7 and Hela cells but both molecules have been found to be largely inactive against HEK-293 cells [55]. The coumarin-linked β-lactam–triazole hybrids 29a,b (Figure 7) displayed modest action for MCF-7 having an IC50 concentration of 53.55 µM and 58.62 µM, respectively, and exhibited

• coumarin phenyl moiety with 4-methoxyphenyl (41a–e) was found to decrease the antiproliferative potency. Furthermore, compounds substituted with para-chloro and para-methyl groups demonstrated potent and wide-ranging anticancer efficacy across multiple cell lines [64]. These studies of coumarin-triazole

• scaffolds 45 (Figure 10) against NCI 60 cells demonstrated broad-spectrum antiproliferative effects of compounds 45a and 45d, having GI50 values from 3.69 to 20.40 µM and 0.29 to >100 µM, respectively [72]. Further examined was the inhibitory activity of selected hybrids against the epidermal growth factor

The surprising reaction of (chloro- and methanesulfonyloxy)(phenyl)methylphosphonates and –(phenyl)methylphosphine oxides with potassium diphenylphosphide followed by oxidation

• Zsuzsanna Szalai,
• Janka Bednárik,
• András Miskó,
• Angéla Takács,
• László Kőhidai,
• László Drahos and
• György Keglevich

Beilstein J. Org. Chem. 2026, 22, 1160–1167, doi:10.3762/bjoc.22.93

• . Cell viability assays performed on U266 myeloma cells revealed concentration-dependent antiproliferative effects of the synthesized compounds on U266 myeloma cells, highlighting the key role of the phosphinoyloxy moiety in the cytotoxic activity, which may be enhanced further by 4-methyl groups in the

• more pronounced antiproliferative effects. Several derivatives resulted in statistically significant decreases in the number of viable cells. (Hydroxy(aryl)methyl)(diaryl)phosphine oxides 14a–d,f and ((methanesulfonyloxy)(aryl)methyl)(diaryl)phosphine oxides 16a and 16e induced only moderate reductions

• -substituent, nor the electron-donating methoxy group enhanced the potency comapared to the unsubstituted 8a. However, the presence of the electron-donating 4-methyl group in the phenyl rings attached to the central P-atom, as in compound 8e, may enhance further the antiproliferative activity. Overall, the

Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive compounds

• Polina A. Man’kova,
• Vadim A. Shiryaev,
• Olga S. Podlipnova,
• Marat M. Khisyamov,
• Dmitry S. Nikerov,
• Alexander N. Reznikov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2026, 22, 1013–1022, doi:10.3762/bjoc.22.80

• cell damage [57], and activity against Staphylococcus aureus was noted for peroxysampsone A С [58]. Basarić and co-workers showed that the replacement of 2-substituted adamantane by a homoadamantane skeleton led to enhanced antiproliferative activity (compound D) [59]. Compound E showed efficacy

Novel macrocycles: from synthesis to supramolecular function

• Veronica Iuliano,
• Carmen Talotta,
• Margherita De Rosa,
• Paolo Della Sala,
• Konrad Tiefenbacher,
• Pablo Ballester and
• Carmine Gaeta

Beilstein J. Org. Chem. 2026, 22, 982–985, doi:10.3762/bjoc.22.76

• amphiphilic calixarene scaffold bearing long alkyl chains, the authors obtained a derivative that spontaneously self-assembles into stable nanoscale aggregates in water. Biological studies revealed a potent antiproliferative effect against human renal carcinoma cells, with limited toxicity toward healthy

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

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

• parent compounds amonafide (4) and mitonafide (5), which have progressed to clinical trials but exhibited unpredictable toxicity [30]. Consequently, recent research has focused on minimising these adverse effects while enhancing antiproliferative potency through diverse synthetic modifications [31]. One

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

• antiproliferative and cytotoxic activity against the tested NCI60 cancer cell lines. Also, several other 7-(1,4-diazepan)- and 7-piperazine-substituted [1,3]oxazolo[4,5-d]pyrimidines (structures A and B in Scheme 1) showed cytotoxic activity in the micromolar concentration range against most breast cancer cell

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

• 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

• in Supporting Information File 1, Figures S77–S79. As can be seen from the obtained results, the compounds generally have a limited antiproliferative effect against these cells in contrast to previously studied compounds that contain a cyclopropane moiety instead of a pyrrolidine one [57] and

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

• activity [33]. Halogen substituents in this position have been shown to modulate antibacterial, antiviral, and antiproliferative activities, likely through electronic effects and improved target binding. The C3 position was functionalized with a propanoic acid moiety, explored in both its open-chain (acid

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ], antioxidant [34], cytotoxic [35], and antiproliferative [36]. The structures of these compounds allow the synthesis of a large collection of bioactive molecules due to their nucleophilic and electrophilic properties [37]. One of the forms of modifications is at the methylene group, particularly in the 5

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

• (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

• confirmed by comparison with the calix[4]arene precursor (1) lacking these functional units. The selective antiproliferative profile of compound 3 highlights its potential as a lead anticancer agent. Moreover, compound 3 holds promise for further development in combination multidrug therapy due to the

• renal carcinoma cells (786O) and normal human fibroblasts (SW1), and the tumor cells selectivity was evaluated. To elucidate the role of the isothiouronium groups, antiproliferative effects were also estimated on calix[4]arene precursor 1 lacking these functional groups. Results and Discussion Synthesis

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• notable DNA intercalation and antiproliferative effects [16][17], while TT–BODIPY derivatives were shown to efficiently generate singlet oxygen and demonstrate light-induced cytotoxicity, highlighting their promise as photodynamic therapeutic agents [18]. Near-infrared TT–DPP-based dyes have also been

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

• polycyclic structures, DNA was not the primary target for their antiproliferative effects, as confirmed by FID assay and fluorescence titration studies. This study represents the first comprehensive evaluation of indolo[1,2-c]quinazolines as potential scaffold for the development of antitumor agents

• , offering valuable insights into their SAR and paving the way for a future evaluation of these compounds as anticancer therapeutics. Keywords: antiproliferative activity; antitumor agents; indolo[1,2-c]quinazoline; modification; structure–activity relationship; Introduction Organic compounds featuring

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

• electrochemical behavior. The compounds were efficiently obtained via the condensation of chlorophosphine oxides and phosphorus oxychloride with glycidol, affording high-purity products in moderate to good yields. Cytotoxicity studies revealed that all three compounds possess antiproliferative activity against

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• : it acts as an antioxidant [28], shows antibacterial activity against Mycobacterium tuberculosis [31], has antiproliferative effects against triple-negative breast cancer [32], serves as an agent against Parkinson's disease [29], and possesses skin anti-inflammatory properties [33]. Notably, the

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

• then elucidated as massarilactone D 4,7-di-O-crotonyl. Cytotoxic and nematicidal activities The antiproliferative properties of massarilactone D and the newly synthesized analogues were evaluated against the murine fibroblasts L929, human cervix carcinoma KB3-1, human lung carcinoma A549, human

• with cinnamoyl chloride suggests that these two polyketides can interconvert from each other and could be artifacts and vice versa formed during extraction and isolation. This finding suggests that, to improve the antiproliferative efficacy of these derivatives, the exo-methylene group should be

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

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

• activity, inhibiting approximately 70% of Staphylococcus aureus biofilms at concentrations as low as 3.9 µg/mL. Keywords: antibiofilm; antiproliferative; beauvericin; insect pathogen; Samsoniella; Introduction A microbial biofilm represents an assemblage of planktonic cells to overcome hostile living

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

• sodium tert-butanolate afforded the desired deprotected indigo-N-rhamnoside 5d (α/β = 2:1). In contrast to the antiproliferative properties of the akashins, 5d showed no significant activity against human cancer cell lines. The glycosylation of 13 can be explained as follows (Scheme 9): Reaction of tetra

• collaboration with Michael Lalk and Patrick Bednarski (University of Greifswald), the antiproliferative activities of indirubin-N-rhamnosides 17a–c,f, indirubin-N-glucoside β-18a, indirubin-N-galactoside β-20a, and indirubin-N-mannoside β-21a were studied. In this context, four human cancer cell lines were

• substituent. The carbohydrate moiety also has an influence on the antiproliferative activity. The best activities were observed for rhamnosides, while the lowest activity was observed for galactoside β-20a. The configuration of the anomeric carbon atom of the rhamnoside did not show a major influence as very

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• properties [28]. Anti-tuberculosis activity was identified for 5-substituted 2-mercapto-1,3,4-oxadiazoles [29], 5-substituted-2-[(3,5-dinitrobenzyl)-sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles [30]. Some derivatives of 5-(4-tert-butylphenyl)-1,3,4-oxadiazole-2(3H)-thione showed antiproliferative

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• high-energy materials [8][9][10][11][12][13]. Moreover, furazan derivatives possess antiproliferative, antibacterial, antiparasitic and antiviral activity [14][15][16]. On the other hand, furoxans referred to as unique heterocyclic compounds that exhibit NO-releasing properties under physiological

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• derivatives (mainly amides) exhibit various types of biological activity, among which the following can be highlighted: inhibition of β-lactamases [4][5], antitubercular properties [6], antiproliferative and antibacterial activity [7], herbicidal properties [8][9], inhibition of neutral amino acid transporter

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

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• heterocyclic moieties containing three or more (hetero)cycles. Moreover, many compounds are accompanied by data on their biological activities, such as antiproliferative, antimalarial, antimicrobial, antifungal, steroid antagonist, and enzyme inhibition, among others, aimed at furnishing pertinent insights for

• et al. reported the synthesis of cycloadducts 47 from reaction of (E)-16-arylidene derivatives 46 and azomethine ylides generated in situ from substituted isatins and sarcosine [27] (Scheme 14). The resulting spiro compounds proved to be potent antiproliferative agents against human cancer cell lines

• promoted by mercury(II) oxide, yielding spiro 2-substituted amino-4,5-dihydro-1,3-oxazoles 72a,b in moderate to good yields (Scheme 21). All spiro derivatives exhibited potent antiproliferative activity when tested on six human cancer cell lines (GI50 = 0.34–18 µM). Structure–activity relationships

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

• , aliphatic chain on the acid component and small aliphatic chain on the aldehyde component to increase the antiproliferative activity. Also, benzyl isocyanide was favored over the aliphatic one (Scheme 1A) [16]. Considering the value of amide groups in drug discovery [19], the feasibility of running the

• . Compounds 5ib and 5hb, with N-Boc protected-heterocycle units in the 5-amide position of the oxindole ring (Scheme 2) failed to afford the corresponding 3-deprotected isatin hybrids, since only decomposition byproducts (not identified) were obtained. Antiproliferative activity Considering the potential

• antiproliferative activity of these compounds, we screened 14 α-acetamide carboxamide isatin hybrids against six human solid tumor cell lines. The panel of cell lines comprised non-small cell lung carcinoma A549 and SW1573, cervical adenocarcinoma HeLa, breast cancer HBL-100 and T-47D, and colon adenocarcinoma WiDr