Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• University, Universitätsstraße 25, 33615 Bielefeld, Germany 10.3762/bjoc.21.40 Abstract Drug conjugates using toxic payloads are a promising approach for selectively combating cancer while sparing healthy tissue. The lack of highly cytotoxic and at the same time selective therapeutics against cancer is an

• ongoing challenge. Cryptophycins are a class of cyclic depsipeptides renowned for their high cytotoxicity in the picomolar range often combined with efficacy against multidrug-resistant tumour cell lines. However, cryptophycins failed as stand-alone drugs in cancer treatment, and their naturally occurring

• particularly effective against multidrug-resistant cancers. Keywords: cancer treatment; cryptophycins; drug conjugates; payload; targeted delivery; Introduction Cryptophycins emerged as highly potent cytotoxins for the use in targeted cancer therapy [1]. Originally discovered over three decades ago by

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• (R01 CA269377) and the UTSW SCCC Breast Cancer Collaborative Pilot.

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• Comprehensive Cancer Center at University of Alabama at Birmingham, Department of Medicine, Section of Hematology/Oncology, Heersink School of Medicine, Birmingham, AL 35233, USA 10.3762/bjoc.21.26 Abstract The acid-catalyzed reaction of benzo[e(g)] derivatives of 2,3,3-trimethylindolenines with o-chloranil

• -(1,1-Dimethyl-1H-benzo[e]indolin-2-yl)-5,6,7-trichloro-1,3-tropolone exhibited high in vitro cytotoxic activity against A431 skin cancer and H1299 lung cancer cell lines. Keywords: cytotoxic activity; fluorescence; o-chloranil; quantum chemical DFT calculations; 1,3-tropolones; X-ray diffraction

• properties towards CN− and Hg2+ ions and evaluation of in vitro cytotoxic activity against A431 skin cancer and H1299 lung cancer cell lines. Results and Discussion We found that boiling of equimolar amounts of benzannelated 2,3,3-trimethylindolenines 2a,b and o-chloranil (3) (method A) in dioxane leads to

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• results showed that out of fourteen synthesized compounds, 7b (MIC90 = 16 μg/mL) and 7h (MIC90 = 8.0 μg/mL) exhibited potent antibiotic activity against different strains of S. aureus (susceptible, methicillin-resistant, and multidrug-resistant). Cytotoxic studies against the human colon cancer mammalian

• pain [48], cancer [41], hypertension (as diuretics) [41], and arthritis [49]. This article introduces a new approach to synthesize the targeted scaffolds from commercially available saccharine without using amide coupling agents to minimize the cost. This work is the first attempt to put pyrazolo-1,2

• improve the antimicrobial potential. Cell viability study Single-dose MTT assays were performed for compounds 7a–n against the human colon cancer mammalian cell line (HCT-116, ATCC CCL-247) for evaluating their inhibition of mammalian cell metabolism [53][54][55]. Solutions of the tested compounds were

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

• the first 2-pyridone derivative, farinosone A (2) that through N-hydroxylation would reveal farinosone B (3). Biological evaluation All the isolated compounds were assessed for their cytotoxic activity against a panel of seven different cancer cell lines. The results (Table 2) revealed that farinosone

• cell lines: mouse fibroblasts (L-929) and human endocervical adenocarcinoma (KB-3.1) applying a previously described protocol [20][21]. Compounds exhibiting cytotoxic properties against these two cell lines were further assessed against prostate cancer (PC-3), breast cancer (MCF-7), ovarian cancer

• (SKOV-3), epidermoid carcinoma (A431) and lung cancer (A-549) cell lines. Epothilone B served as the positive control. Following a 5 day incubation period, the minimum concentration required to achieve 50% growth inhibition (IC50 values) was determined. Biofilm inhibition sssay Biofilm inhibition

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• results in one case, providing high cytotoxicity toward the MCF-7 cancer cell line. The stable axial chirality of the products 71 and 73 was confirmed by calculations of the rotational barriers ranging from 30.2 to 46.3 kcal/mol. Kinetic resolution by amino group protection of biaryls (R,S)-74a–r with

• and stereoselectivities (85%, 90% ee, >95:5 E/Z). A biological activity investigation led to promising results in the case of one substrate displaying cytotoxicity towards several cancer cell lines. Organocatalytic enantioselective construction of axially chiral styrenes 175 and 177 was done utilizing

• enantiopurity at 130 °C for 48 h in toluene. Investigating the biological activity for a number of compounds, good cytotoxicity was reported for five kinds of cancer cells. The mechanistic study suggests that the indole ring of the substrate is having a crucial role in the reaction mechanism because replacing

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• areas, including lifespan extension, obesity, age-associated diseases, neurological function, cardiovascular disorders, and cancer. Notably, the inhibition of sirtuin 2 (SIRT2) has demonstrated protective effects in both primary neuronal cultures and invertebrate models of PD [48]. SIRT2 is present in

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

• efficiency and creating six new bonds (two C–C, three C–N, and one N–N). Additionally, the products were evaluated against breast cancer MCF-7 cells, finding moderate activity in the compounds substituted with fluorine and chlorine. Keywords: 1,5-disubstituted tetrazoles; high-order multicomponent reaction

• cytotoxic compounds. For example, a cytotoxic effect was found in CAL 27 cells, presumably through a mechanism of TNF-α inhibition in vitro, which could be related to the anti-inflammatory effect identified in several studies of NSAIDs that inhibit cancer cell viability in vitro [37][38]. In another study

• against MCF-7 cell line, which has been used as a model for breast cancer (BC), a public health issue very common and a deadly pathology worldwide, where women between 45 and 55 years of age are the most vulnerable population. In 2020, 684,996 deaths were recorded [40][41][42][43]. This in vitro

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

• their activity against various types of cancer. N-Glycosides of indigo, indirubin, and isoindigo, blue, red, and yellow sugars, turned out to be of special interest because of their high cancerostatic activity and structural novelty. The present article provides an account on the synthesis and

• [12][13]. In addition, there are more and more applications in the field of medicinal chemistry, especially for the treatment of cancer [14][15]. In the course of the renewed interest in the chemistry of indigo, indirubin, and isoindigo in the field of cancer research, N-glycosides of these compounds

• exhibit an absorption at 618 nm and show a blue color. In contrast to biologically inactive indigo, akashines A–C are active against various human tumor cell lines (CNCL SF268, LCL H460, MACL, colon carcinoma CCL HT29, melanoma MEXF 514L, lung carcinoma LXFA 526L and LXFL 529L, breast cancer MCF-7, kidney

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• in MeOH at room temperature with a short reaction time. Some of them were further functionalized with a 1,2,3-triazole ring via copper-catalyzed azide–alkyne cycloaddition (CuAAC) and deprotected with trifluoroacetic acid. Several hybrids were evaluated against six cancer cell lines, displaying GI50

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• this paper, we report a short and efficient synthesis of novel N-arylbenzo[h]quinazoline-2-amines. We have prepared a focused library of nineteen representative examples which have been submitted to cytotoxicity assays against a representative panel of eight cancer cell lines and several molecules gave

• Next, we performed a cytotoxicity screening of the nineteen molecules 4a–s, at 25 μM, investigating seven representative cancer cell lines: hepatocellular carcinoma HuH-7, colorectal adenocarcinoma CaCo-2, breast carcinoma MDA-MB-231 and MDA-MB-468, colorectal carcinoma HCT-116, prostate carcinoma PC3

• ) exhibited a relatively broad cytotoxicity on four cancer cell lines among the seven assayed. On the other hand, two others (4f and 4h) were active only on Caco-2, while another one (4d) only on HCT-116. Thus, the results obtained with these compounds indicate that such a novel heterocyclic scaffold, which

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

• activity against the HeLa cancer cell line [22]. 1,2,4-Triazole thioglycoside derivatives have antiviral activity against influenza strains H3N2 and H5N1 [31][32]. The 1,2,4-triazole-3-thione-imidazole hybrids displayed potential antibacterial activity against E. coli, S. aureus [33]. Heterocyclic thione

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• -methylalternariol derivative 15 was isolated from A. alternata and showed inhibitory activity against HCV NS3/4A protease (IC50: 52.0 μg/mL), cytotoxic activity against HEP-G2 cancer cells, and turned out to be antibacterial against Bacillus cereus, B. megaterium, and Escherichia coli with inhibition zones of 17

• weight) [11][74], and showed toxicity against brine shrimp larvae (Artemia salina) with an LD50 value of 375 µg/mL [256][257]. It exhibited cytotoxicity against HeLa cells (ID25: 28 µg/mL) [74], the HCT116 cancer cell line (IC50: 3.13 μM) [232], and against MG-63 cells (IC50: 17.8 µg/mL) [123]. An

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• activity and thus block cancer formation [2]. Alangiumkaloids A, an isoquinolinone alkaloid isolated from Alangium salviiforlium, was reported to exhibit cytotoxic activity against cancer cells [3]. In 2018, duvelisib, a dual inhibitor of phosphoinositide-3 kinases, was firstly approved by the FDA for the

• treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma [4]. Palonosetron is a key component of Akynzeo®, used for the prevention of acute and delayed nausea and vomiting of cancer patients who are receiving chemotherapy [5]. As an active compound

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• hydration reaction of carbon dioxide to bicarbonate, cyanates to carbamic acids, aldehydes to gem-diols, etc., and represent a potential therapeutic target for diseases like osteoporosis, edema, obesity or cancer [29]. Alım et al. [30] evaluated a series of thiophene sulfonamides based on the high stability

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

• 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

• . Chromatographic purification was not required post-reaction. Some spiro products exhibited high binding affinity towards DNA, while others showed good cytotoxicity against different cancer cells (A545, MCF-7, HeLa, HL-60, SW480, HepG2, HT-29, and A549) with IC50 values within the micromolar range (2.18–18.54 µM

• 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

• lines, among them, non-small cell lung carcinoma, cervical adenocarcinoma, breast cancer and colon adenocarcinoma. The most potent compounds 8d, 8h and 8k showed GI50 values in the range of 1–10 μM. Keywords: cancer; GI50; isatin; oxindole; Ugi4CR; Introduction Meticulous attention has been given by

• agents [14][15][16] (Figure 1). Cancer is a complex, cureless and fatal disease, oftentimes diagnosed worldwide. Being one of the leading causes of death worldwide, it is expected an increase of 47% with 28.4 million cases diagnosed, in 2040 [17][18]. Despite long years of research, there is still an

• urgent need to find novel, effective and safe drugs for cancer therapy. Recently, focusing on the design of more potent anticancer drug candidates using more sustainable synthetic processes, we report a new Ugi four-component reaction approach for easy access to Ugi-derived isatin-peptoids in moderate to

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• biological activities [1][2]. Notably, kinamycins demonstrate both antibacterial and antitumor activities, while lomaiviticin emerges as a potent antitumor agent, displaying remarkable IC50 values ranging from 0.007–72 nM against 25 cultured human cancer cell lines [3][4][5][6][7]. The pivotal B-ring

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells. Keywords: bismuth; catalysis; heterocycles

• reaction temperature. The initial biological profile of 20 indanones was assessed, revealing promising activity against certain human cancer cell lines in some cases. To enhance the anticancer potential of these compounds, it is imperative to carry out additional comprehensive studies. Examples of

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

• nuclear and mitochondrial genomes [15]. This A3-induced mutational activity is used by viruses and cancer cells to increase the rates of mutagenesis, which allows them to escape adaptive immune responses and become drug resistant [16][17][18][19][20], leading to poor clinical outcomes. A range of genetic

• partially localised in the nucleus of cells and, in cancer cells, become genotoxic [24]. A3A and A3H are single-domain enzymes, whereas A3B is a double-domain enzyme, in which only the C-terminal domain (CTD) has catalytic activity, and the N-terminal domain (NTD) is responsible for binding of DNA and for

• with reduced tamoxifen sensitivity of tumours in those patients [19] and poor survival rates for estrogen receptor-positive (ER+) breast cancer patients [21][29]. In line with these observations, A3B overexpression accelerates the development of tamoxifen resistance in murine xenograft with ER+ breast

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• inhibitor of homeodomain-interacting protein kinases (HIPKs) [32], and combretastatin A-4 analogs evaluated for their anticancer properties against a panel of 60 human cancer cell lines [33] (Figure 2). The structures of all new compounds were confirmed by 1H and 13C NMR and HRMS. X-ray diffraction studies

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• -based probes; Introduction To date, natural products and their derivatives have served as the foundation of many pharmaceuticals used today. These compounds have activity against various diseases such as cancer, bacterial infections, and fungal infections, as well as other indications [1]. Specifically

• . Alkhalaf (University of Warwick), and C. Corre (University of Warwick) for providing us with the Streptomyces strains. Funding This work was supported by a grant from the National Institutes of Health (1R35GM138002-01 to E.I.P.). The authors acknowledge the support from the Purdue Center for Cancer

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• research has been also supported (AD) through the ERA Chair grant ACCELERATOR (101087318). This study was supported by the National Institute for Cancer Research–Programme EXCELES (ID Project No. LX22NPO5102), funded by the Cancer Research Czech Republic.

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• biosensors, bioimaging probes, and especially as photosensitizers (PSs) in photodynamic therapy (PDT) [2]. PDT is a treatment modality that uses the combination of a non-toxic PS, oxygen, and light to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections

• molecules which have been also used for selective delivery of the drug to cancer cells [45]. Here, biotin was conjugated to porphyrin 12 which was obtained by alkylation of the amino group in compound 5 with chloroacetyl chloride (10) to give porphyrin biotin conjugate 14 in 76% yield (Scheme 4). We also