Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• lymphoma 2 (bcl-2) protein levels were examined. All PS-ASOs gave improved downregulation relative to the control (scrambled sequence), but only PS-ASOs carrying the nucleotides modified with spermine (i.e., monomer 49) or pentaamine (i.e., monomer 50) induced improved downregulation of gene expression

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

• localization signal (NLS) peptide (PKKKRKV, Figure 12A), and showed that the PNA–NLS conjugates localized predominantly in the nucleus rather than in the cytoplasm of Burkitt's lymphoma cell lines (BRG, BJAB, HBL2) [172]. The opposite trend was observed for unmodified PNA or PNA conjugated to a scrambled-NLS

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

• shown promising biological activities in preclinical and clinical studies (Figure 1) [2][3][4][5][6]. The pyrimidine-γ-carboline alkaloid ingenine B (isolated from an Indonesian sponge) exhibits a pronounced cytotoxicity against a murine lymphoma cell line [7] and several isocanthine analogs are

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• overall steps [164]. ASOs containing these modified nucleosides have demonstrated promising antitumor activity for lymphoma and lung cancer [165]. Numerous other LNA analogues have been constructed including, but not limited to, 2'-N-guanidino,4'-C-ethylene (GENA) (Figure 7I) [166], sulfonamide-bridged

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• of thiazolidinedione were used to study the cytotoxic activity in comparison with camptothecin and etoposide on Jurkat, K562, HEK293, HELA, A549 and U937 cell lines. Compounds 20 and 17 showed the highest activity (IC50 = 0.29 and 0.36 nM, respectively) for leukemic monocytic lymphoma cells (U937

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

• refractory cutaneous T-cell lymphoma (CTCL) [3]. Moreover, it also shows anticancer activity against a large number of hematological and solid malignancies [4][5]. Its anticancer activity is related to inhibition of histone deacetylase inhibitor (HDACi) at nanomolar concentrations (IC50 < 86 nM). Although

• hydroxamic acid derivative belinostat (2) is also approved for the treatment of peripheral T-cell lymphoma (PTCL) [9]. On the other hand, trichostatin A (3), containing an α,ß-unsaturated hydroxamic acid unit is the best known HDAC inhibitor which shows antifungal activities [10][11]. Because of the

• ], B cell lymphoma (A20 cells) [28], and head and neck squamous cell carcinoma (HNSCC cells) [29], among others. The mechanism of biological action of SAHA in different types of cells is indeed plural in nature. Some of the common cell death pathways are intrinsic and extrinsic apoptosis [30], ROS

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• approved drug for cutaneous T-cell lymphoma); NCIH460 = lung cancer cell line; HCT116 = colon cancer cell line; U251 = glioma cell line. Structural modifications on the 4-oxo-1,4-dihydroquinoline-3-carboxamide scaffold. Same scale partial 1H NMR spectra of compounds 5 and 7 (DMSO-d6, 500 MHz). 1H,1H-COSY

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

• =Aoa) could be attributed to the presence of butyrate, which has been demonstrated to inhibit the proliferation as well as to induce apoptosis and cell cycle arrest in different cell lines (e.g., colon carcinoma, melanoma, T-cell lymphoma) as a histone deacetylase inhibitor and/or via activation of

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

• promyelocytic leukemia cells) tumor cell line and 0.58 μM for U937 (Human leukemic monocyte lymphoma cells) tumor cell line with reduced toxicity in comparison to paclitaxel and 5-FU [116]. Ivanov et al. reported two different sets of strong minor groove binders, derived from well-known DNA minor groove binder

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• and Preston reported the synthesis of the antibody–drug conjugate (ADC) α-amanitin-anti-Thy 1.2 IgG, which was 47-fold more toxic than the unconjugated α-amanitin in the murine T lymphoma S49.1 cell line [4]. In 2012, a new ADC containing α-amanitin and a chimerized anti-EpCAM (epithelial cell

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• the potential bioactivity of fluorine, an investigation was conducted using various fluorine-containing diaryliodonium salts in order to study and compare their biological activity against human lymphoma U937 cells. Most of the compounds tested are well-known reagents for fluoro-functionalized

• )phenyl)iodonium exhibited the greatest potency in vitro against U937 cells. Evaluation of the cytotoxicity of selected phenylaryl-λ3-iodonium salts against AGLCL (a normal human B cell line) was also examined. Keywords: biological activity; diaryliodonium salt; fluorine; hypervalent iodine; lymphoma

• to investigate a biological study of fluorine-containing hypervalent iodine compounds in vitro using U937 (a human histiocytic lymphoma cell line) [55][56][57][58]. The U937 cell line is maintained as replicative non-adherent cells having many of the biochemical and morphological characteristics of

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• cytotoxic activity toward lymphoma cells, resulting active at a very low micromolar range [101]. With the aim to activate the human immune system against self-tumor cells, Schlecht and co-workers designed the synthesis of AuNPs functionalized with Mucin1(MUC1)-glycopeptide antigens [102]. Mucins are a

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• metastatic breast cancer treatment, demonstrating the therapeutic potential of myxobacterial secondary metabolites [29][30][31]. This drug has also been assessed as chemotherapeutic agent in pancreatic lymphoma showing promising results and tolerable toxicity [32]. Over time, different strategies have been

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• for 18 [22]. Further, alternariol (17) and derivatives were tested against L5178Y mouse lymphoma cells. Here 17 was the most active compound with an EC50 value of 1.7 μg/mL [23]. In another in vitro assay, this time a biochemical assay using protein kinase, the IC50 values were determined, and 17

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• isolated in 1994 from Reniera mucosa alongside its non-cyclised isomer 1, and ten other members of the panicein family [3]. Panicein A2 (5) and D (2) were reported to exhibit in vitro cytotoxicity against four cancer cell lines (P388 mice lymphoma, A549 human lung carcinoma, HT29 human colon carcinoma and

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• ) – inhibitors of thymidine phosphorylase isolated from spontaneous lymphoma of SD rats (IC50 = 15 and 11 nM, respectively) [4], guanine derivative 5 – a potent inhibitor of human purine nucleoside phosphorylase PNP (Ki = 10 nM) [5], and finally guanine derivative 6 – exhibiting inhibitory activity against 6

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• results of the lymphoma cell line BJAB. Cell surface transmembrane receptor CD95, through which apoptosis can be induced, is expressed by BJAB cells. Cell death can be induced in these cells both by the extrinsic and the intrinsic apoptosis-signalling pathway [47][48][49]. Therefore, BJAB cells are well

• apoptosis. So we determined the AC50 values of our titanocenes, i.e., the concentrations causing specific apoptosis in 50% of lymphoma cells, counting all cells with membrane damage. The azide-substituted complexes showed no significant apoptosis induction (AC50 > 100 µM). Introduction of the triazole ring

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• the treatment of multiple myeloma and mantle cell lymphoma [21]. This product is usually synthesized in three representative processes: (1) to use (1S,2S,3R,5S)-(+)-2,3-pinanediol as the chiral auxiliary for the addition reaction followed by chlorination and amination [14][15]; (2) to perform copper

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• treatment of Hodgkin lymphoma (Brentuximab vedotin) [4]. In this paper, we report the first total synthesis of malevamide D (1) and an assessment of its in vitro cytotoxicity in a panel of 42 cell lines. We also synthesized a diazirinylated analog of 1, which, by photocrosslinking, might contribute to the

• determined IC50 values of about 0.7 nM against four cell lines (mouse lymphoma P-388, human lung carcinoma A-549, human colon carcinoma HT-29, human melanoma MEL-28) [1]. We had hoped that introduction of a Brunner-type diazirine unit in the para-position of the phenyl ring of 1 could lead to an analog that

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• ], lymphoma [17][18][19], multiple myeloma [17][20], and chronic myeloic leukemia [21][22][23]. More recently, other diseases like diabetes [24][25], neurodegenerative disorders [26], and trisomy [27][28], have been linked with hedgehog signaling. Cyclopamine (1, see Figure 1) was the first inhibitor of the

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• ][3][4]. Biological assays revealed that 1 exhibits cytotoxicity against murine lymphoma L1210 and human epidermoid carcinoma KB cells (IC50 = 0.46 μg/mL and 1.7 μg/mL, respectively) [1]. Moreover, 1 has been shown to promote nerve growth factor biosynthesis in 1321N1 human astrocytoma cells [2]. In

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• ® NHS-LC-LC-Biotin, DIEA, DMF, 35 °C or rt; (d) EZ-Link® NHS-PEG4-Biotin, DIEA, DMF, 35 °C or rt. Reagents and conditions: (a) 6-Boc-aminocaproic acid, DCC, DMAP, CH2Cl2, rt; (b) TFA, CH2Cl2, rt; (c) D-biotin, DCC, DMAP, CH2Cl2, sonicate. Acknowledgements G.C. is funded by Leukemia and Lymphoma Society

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• name Zolinza by Merck & Co.) and romidepsin 2 (trade name Istodax by Celgene) for the treatment of cutaneous T-cell lymphoma (CTCL, Figure 1) [12][13][14]. The success of these compounds in the clinic has led to a significant interest in the further discovery of structurally novel HDAC inhibitors that

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• protein fragment (likewise claimed to enhance membrane permeability) was much less effective (data not shown). Beside mouse fibroblasts, we investigated the phalloidin derivatives in several human leukemia and lymphoma cell lines, in order to find possible specificities for one or the other kind of tumor

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• inactive, small amounts of Neu5Gc 2 are also found in the human metabolism presumably dietary derived from carbohydrate salvage pathways [5][6]. The efficient uptake and incorporation of sialic acid modified in positions C-5 and C-9 into human B-lymphoma cells (BJA-B), Jurkat and others including primary