Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

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

• with a standard drug, doxorubicin, were screened for their cytotoxicity against various cancer lines (Figure 5, Table 3 and Figure S2, in Supporting Information File 1) such as MCF-7 (breast cancer), HeLa (cervical cancer), HEK293 (human embryonic kidney cells), A431 (skin cancer), A549 (lung cancer

• , 3ca, 3ga in the breast cancer cell line, MCF7 and (B) doxorubicin against the panel of tested cancer cell lines. Dose–response curve of γ-carbolines 3ac, 3bc, 3ca, 3ga in macrophage cell line, RAW264.7. Laser scanning confocal microscopy studies (λex = 405 nm; collection range = 420–470 nm) for uptake

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• pancreatic carcinoma and triple-negative breast cancer (Scheme 23B) [55]. Konteatis et al. adopted a similar approach by using the direct fusion for the preparation of bisdifluorocyclic biguanides as IDH1/2 inhibitor intermediates (Scheme 23C) [56]. However, sodium dicyanamide has been mainly used as an

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• their LNP formulation to functionalize LNPs with an aptamer specific for the human epidermal growth factor 2 (HER2) receptor. Therein, functionalized LNPs increased siRNA delivery and subsequent sensitivity of the doxorubicin-resistant HER2-positive breast cancer cell lines by ≈2-fold over LNPs with no

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• disorders of ganglioside biosynthesis can lead to a number of neuropathies, including motor deficits, microcephaly, sensory loss, and autistic features [10][11]. Certain gangliosides, such as GM2, have been identified as tumor markers for breast cancer stem cells [12], while members of the alpha-series

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

• production [11] that plays an important role in the growth of various cancerous tissues (colon, lung, and breast cancer) and as antagonists of the human A3 adenosine receptor [12]. Aminophthalazines have been also evaluated for their inhibitory activity toward phosphodiesterases such as PDE-5 (Figure 1) [13

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• a low (1 mol %) catalyst loading, to obtain enantiomerically enriched β-naphthyl-β-sulfanyl ketones with up to 96% ee. The target adducts are the core structure of seco-raloxifene derivatives, which are potent anti-breast cancer agents [32]. In addition, the same scaffold has also shown urease

• , which have potent activity against breast cancer. The easy access to the corresponding sulfones presents a versatile route for the implementation of a new biologically active moiety, the sulfone, to the β-naphthyl-β-sulfanyl ketones. The enantioenriched products of both classes can be evaluated as

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• presence of DNA, and another intrinsically disordered binding partner, breast cancer antigen 1 (BRCA1) (Figure 12). In this work the strategy employed involved the introduction of a perfluorinated [19F]3,5‐bis(trifluoromethyl)benzyl-based tag into the single cysteine residue of Myc. This modification

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• epithelial cells, the mixture of O-glycans that glycosylate mucins are extended core 2 structures, while in breast cancer cells, O-glycan mass decreases (hypoglycosylation), and there is an increase in abundance of sialylated core 1 [15]. The upregulation of Tn (αGalNAc) and STn (αNeuAc-2,6-αGalNAc) antigens

• breast cancer [11][13]. We use MD simulations to investigate the conformational behavior of (glyco)peptide antigens bound to the AR20.5 antibody and to investigate the hypothesis that the glycan modulates the conformation of the peptide portion of the antigen. Primarily showcasing a structural analytics

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• heterocycle is present in several alkaloids such as emetine (1) and related compounds, that exhibit biological activities such as glucosidase inhibition, anti-amoebic properties as well as activity against breast cancer cell lines [2]. Notable examples of synthetic compounds include the dipeptidyl peptidase

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• hexacarbonyls with 2'-deoxyuridines revealed pronounced in vitro activity against MCF-7 and MDA-MB-231 human breast cancer cells [32][33]. A recent investigation of hexacarbonyl dicobalt adducts of nucleosides containing derivatives of propargyl alcohol demonstrated their antiproliferative activities for the

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• three steps. Biological studies Although approved for the treatment of CTCL, SAHA has been shown to display anticancer activity over a large range of other hematological and solid malignancies such as leukemia [24], lung cancer [25], cervical cancer (HeLa), breast cancer (MCF-7) [26], mesothelioma [27

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• shown in Figure 11 was tested in vitro on human breast cancer cells MCF-7. One-photon absorption induced fluorescence demonstrated that this dendrimer is efficiently internalized after 3 h of incubation, more after 24 h, and was non-toxic at 50 μg mL−1 without irradiation. Two-photon irradiation was

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• following cell lines were used: mouse fibroblast cell line L929 (DSM ACC 2), human cervix carcinoma cell line KB-3-1 (DSM ACC 158), the human lung carcinoma cell line A549 (DSMZ ACC 107) and human breast cancer cell line MCF-7 (DSM ACC 115). The subconfluent cells were briefly washed with Earle’s Balanced

• ppm, J in Hz). For carbon numbering see Figure 1 and Figure 2. Antiproliferative activities in different cell lines. Data indicate EC50 values ± SD in µM. A549 = human lung carcinoma; L929 = mouse fibroblast; KB-3-1 = human cervix carcinoma; MCF-7 = human breast cancer cell line. Supporting

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• lines – luminal A breast cancer cell line MCF7 and triple negative breast cancer cell line MDAMB231. The results were compared with those obtained on normal breast epithelial cell line (MCF-10A). All compounds showed low cytotoxicity on all tested cell lines (for Figure S81 see Supporting Information

• fluorescence quantum yield to 74% in the case of 7-deazapurine derivative 11c. The solvent change provided a fluorescence shift from dark blue (≈440 nm) to orange (≈620 nm) color. Finally, the purines and 7-deazapurines were tested in live cell imaging on breast cancer cell lines MCF-7 and MDAMB231. They are

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• (Ewing`s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chemically transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic

• triple-negative breast cancer MDA-MB-468 cells. Keywords: drug targeting; neuropeptide Y; PDC; peptide–drug conjugate; targeted tumor therapy; tubugi; tubulysin A; Ugi reaction; Introduction Until recently, the medication of tumor diseases was primarily based on more or less unspecific

• breast tissue was found to express negligible amounts of hY1R but predominantly the closely related Y2 receptor subtype (hY2R) [23]. Hence, a switch from hY2R to hY1R expression during pathogenic breast-cell transformation was hypothesized. Furthermore, many breast cancers of all major breast cancer

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• organic anion transporting polypeptides (OATP) protein family [3][4]. Human OATP2B1 is one of the OATPs transporting estrone 3-sulfate, expressed in the intestine, blood–brain barrier, liver and placenta [5][6][7][8][9]. Moreover, OATP2B1 is overexpressed in certain malignancies, including breast cancer

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• and Sjogren's disease are caused by activated macrophages [16]. Recently EC17, (λex = 465–490 nm and λem = 520–530 nm) a conjugate of folic acid and fluorescein isothiocyanate has been used for intraoperative surgery of ovarian cancer [17], lung adenocarcinoma [18][19][20], and breast cancer [21

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• '-ones and their deacetylated analogs were screened on three human adherent breast cancer cell lines (MCF7, T47D and MDA-MB-231): the microculture tetrazolium assay revealed that some of the presented derivatives exerted cell growth inhibitory effects on some of these cell lines comparable to those of

• antiproliferative effects were determined by means of the MTT assay [20] on a panel of adherent breast cancer cell lines (MCF7, T47D and MDA-MB-231) after treatment for 72 h (Table 2). All compounds were initially screened at 10 and 30 μM concentrations and for those compounds that elicited growth inhibition of at

• situ liberation of the reagent from its salt in EtOH followed by the heterocyclization reaction through the addition of AcOH. Some of the presented compounds 6h, 7f, 7i and 7j exerted considerable antiproliferative activity with promising cancer selectivity on a panel of human breast cancer cell lines

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• lines (e.g., colon [20], breast cancer cells [21]). Based on a former receptor binding experiment, the conjugates with Lys(Ac) or Lys(Bu) have a more suitable structure for receptor binding, which is even more preferential in case of the butyryl side chain; however, the even longer side chain linked to

• depending on the cellular milieu or function, the GnRH analogs could elicit different – even opposite – actions [6][40]. For example, Aguilar-Rojas and his co-workers reported a similar combination of actions (invasion inhibitory and adhesion increasing effects) of a GnRH agonist in a breast cancer cell

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• , Cambridge, 02139, MA, United States of America 10.3762/bjoc.14.144 Abstract About 1 in 8 U.S. women (≈12%) will develop invasive breast cancer over the course of their lifetime. Surgery, chemotherapy, radiotherapy, and hormone manipulation constitute the major treatment options for breast cancer. Here, we

• low as 12.5 μmol L−1 for the selective targeting of MCF-7 breast cancer cells. Flow cytometry assays further revealed that treatment with wild-type (WT) peptide Dec-NH2 led to necrosis of MCF-7 cells. Additional atomic force microscopy (AFM) measurements indicated that the roughness of cancer cell

• conformational propensity led to peptide inactivation, whereas increasing the net positive charge of peptides enhanced their activity. We present peptide templates with selective activity towards breast cancer cells that leave normal cells unaffected. These templates represent excellent scaffolds for the design

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• helps to compare cytotoxic efficacy (IC50) of the 15 GnRH-based antitumor conjugates in 3 reference tumor cell lines representing the most frequent malignancies (breast cancer – MCF-7, colorectal adenocarcinoma – HT-29 and acute monocytic leukemia – MonoMac6). In parallel, the cardiotoxic effects of the

• cases the breast cancer (9) or colorectal adenocarcinoma (9, 13) proved to be also sensible to the Dau containing conjugates. On the other hand there are even sad lessons of the comparative study, some mainly Dox containing conjugates (1–3) proved to have strong cardiotoxic effects; however, they had

• antitumor cytotoxic characteristics of the conjugates in human breast cancer (MCF-7), human colorectal adenocarcinoma (HT-29) and human acute monocytic leukemia (MM6) derived cell lines as representative tumor cells. Human cardiac myocytes (HCM) and human umbilical vein endothelial cells (HUVEC) as the

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• composites loaded with quercetin may show improved cytotoxic activity towards some human breast cancer cell lines [32], likely due to a synergistic action between the polyphenol nutraceutic guest molecule and triazole derivatives coming from the progressive disgregation of the co-polymer carrier. From the

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• chimera were investigated. Therefore, we chose two different cancer cell lines, namely breast cancer MCF-7 and cervix carcinoma HeLa cells, which were exposed for 24 h to various concentrations of the peptides sC18*, N50, N50-sC18*, NrTP and NrTP-sC18* (Figure 2). We observed no toxic effects of the

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• . Szerszenowicz et al. developed a new set of potential minor groove binders derived from netropsin and bis-netropsin analogs by replacing N-methylpyrrole rings with other heterocyclic rings and their antiproliferative activity was tested on MCF-7 breast cancer cells [60]. Suckling et al. recently designed and

• DNA binding affinity as well as antiproliferative effects on human MCF-7 breast cancer cells were evaluated [99]. These conjugates bind within the minor groove of B-DNA. They inhibited catalytic action of endonucleases in A·A, A·T, T·T and A·G restriction sites but failed to block G·C-rich sequences

• . In addition, they act as potent topoisomerase II inhibitor at the concentration 10 μM and show antiproliferative and cytotoxic activities in breast cancer cell line in the range of 81.70 μM and 200.00 μM. Conjugate 41 with a 6-aminophenyl moiety appeared to be the most effective among others