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

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• catabolic degradation of proline plays an important role in the development of cancer cells, making the inhibition of the proline dehydrogenase a promising method in cancer therapy [69][70]. There is no information on a possible intracellular degradation of fluoroprolines, although, they are included in

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• cytotoxic against a variety of cancer cell lines, and both bohemamine and NP25302 inhibit HL-60 cell adhesion to Chinese hamster ovary cells expressing intercellular adhesion molecule ICAM-1 (CD-54). This interest led us to develop a total synthesis of NP25302 [25] and its 5-normethyl analog and, 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

• investigated in the presence of cell extracts. Ojima and collaborators have also employed functional ligand-observed NMR experiments to develop a range of novel 3′-difluorovinyltaxoids, such as BLT-F2 and BLT-S-F6 (Figure 5c), that are active against drug-sensitive and multidrug-resistant (MDR) human cancer

• 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

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• biosynthesis [1][4], in vitro antimicrobial activity [4][5], and anticancer activity against human prostate cancer cell lines [6][7]. A recent study suggested that the close analogue (+)-11 of inthomycin C was found to exhibit proteasome inhibition activity [8]. The skeletal structures of inthomycins A–C (1–3

Control over size, shape, and photonics of self-assembled organic nanocrystals

• Chen Shahar,
• Yaron Tidhar,
• Yunmin Jung,
• Haim Weissman,
• Sidney R. Cohen,
• Ronit Bitton,
• Iddo Pinkas,
• Gilad Haran and
• Boris Rybtchinski

Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5

• Current address: Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA, U.S.A. Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel Department of Chemical Engineering, Ben-Gurion University, Beer Sheva 84105, Israel Ilse Katz Institute

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• fundamental in proteomics, and the identification of PPIs has the potential to confer new drug targets for diseases, such as cancer. As a result, research involving PPIs is imperative for our biological knowledge and future aspects in medicine. Different methodologies employed to study PPIs. The protein used

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• effects including cytotoxicity against cancer cell lines, antineuroinflammatory activity, and potential neurotrophic effect were evaluated. Keywords: antineuroinflammation; Chaenomeles sinensis; cytotoxicity; megastigmane; neurotrophic effect; Introduction Chaenomeles sinensis (Thouin) Koehne (Rosaceae

• . Cytotoxicity of compounds 9–11 against four cultured human cancer cell lines in the SRB bioassay. Inhibitory effects of compounds 1–12 on the NO production in LPS-activated BV-2 cells. Effects of compounds 1–12 on the NGF secretion in C6 cells. Supporting Information Supporting Information File 398: 1D and 2D

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• involved in a variety of human diseases like cancer, Alzheimer’s, and Parkinson diseases etc. [46]. Therefore, the Schmuck group in collaboration with the Ottmann group sought to develop fluorescent probes (7 and 8) for monitoring of 14-3-3 proteins (Figure 7) [47]. These probes contain two symmetric GCP

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• ; polyfluorinated carbohydrates; polyfluoroalditol analogues; Introduction The biological significance of carbohydrates includes, but are not limited to, immune regulation, infection, and cancer metastasis. Research in the field of molecular biology allowed the discovery of glycomimetics to study various

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range. Keywords: antiproliferative activity; 1,2-dihydropyridines; green Hantzsch synthesis; heterogeneous catalysis; one-pot multicomponent

• the general procedure. Biological screening The 1,4-DHP scaffold displays an extensive range of biological activities, including reversing multidrug resistance (through the inhibition of the P-glycoprotein) [26] and antiproliferative effects on human cancer cell lines [27]. We wondered whether the

• , the reaction was left to carry on but stopped, and therefore catalyst leaching was not evident. Antiproliferative tests We selected the cancer cell lines A549 and SW1573 (nonsmall-cell lung), HBL-100, as well as T-47D (breast), HeLa (cervix), and WiDr (colon) to evaluate the antiproliferative activity

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• several human cancer cells, but has only a relatively low cytotoxicity in healthy cells [31][32]. Berberine is also known as a G4-DNA ligand [33]. Especially berberine derivatives that carry additional substituents with varying alkyl chain lengths in the 9- and 13-position show enhanced binding properties

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• reversibly change the properties of the cell. For example, we have shown that synthetic receptors appended with a thiol or a folate group enable bacteria expressing the His-tagged outer membrane protein C (His-OmpC) to bind to gold surfaces or cancer cells, respectively [2]. We have also shown that this

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• , peptide assemblies are being explored for a wide range of applications, including cell cultures [6], tissue engineering [7], drug delivery [8][9][10][11], antibacterial agents [12][13], regarding biomineralization [14][15], as collagen mimics [16], anisotropic hydrogels [17][18], for cancer therapy [19

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 cancers [8]. Further, it is thought to participate in the hyperactivation of selected intracellular signal transduction pathways that promote tumorigenicity [9]. MUC1 is a cancer biomarker that can be detected by serum biomarker assays (such as the CA15-3 test [10][11]). The mode of binding

• 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

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• cancer cell growth. Ruthenium(II) tris(bipyridine) (RuII(bpy)3) complexes carrying multiple carboxylate-substituted arms were designed as protein surface mimetics, exploiting electrostatic binding through multiple contacts to the protein surface [63]. 15N-HSQC titrations showed that these complexes

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• blood group antigens (A, B, O), which are glycan structures found on blood cells and tissues that play a critical role in determining transfusion compatibility during blood and organ donation [3], sialyl-LewisA antigen, known more commonly as CA19-9, which is a known tumor marker for pancreatic cancer

• , and could possibly promote cancer [4], and the O-glycan of PSGL-1 which is recognized by P- and L-selectin, which is critical for leukocyte recruitment [5][6]. Other roles of glycans (including glycosaminoglycans/proteoglycans) and glycan binding proteins (GBPs) (including lectins and antibodies) in

• biological systems have been discovered with respect to cancer, infectious diseases, and genetic disorders [7][8][9][10][11][12][13][14][15]. As a technology to study glycan recognition by GBPs, glycan microarrays offer an invaluable tool, and permit examination of all types of lectins, along with antibodies

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• atoms, including drugs used to treat cancer, HIV, smallpox and malarial infections (Figure 1) [5][6]. Moreover, fluorine atoms and trifluoromethyl groups have dramatic effects on the biological activity of agrochemicals, such as herbicides, insecticides and fungicides, as reflected by a plethora of

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• Fisher) and Byonic (Protein Metrics), to extract occupancy and glycoform abundancy of all identified glycopeptides from LC–MS/MS datasets. We applied the workflow to a published dataset comparing the plasma glycoproteomes of liver cancer patients (heptatocellular carcinoma, HCC) and healthy controls [20

• depleted of six abundant proteins from liver cancer (hepatocellular carcinoma (HCC)) patients and healthy controls. We identified glycopeptides and peptides in the datafiles from these samples using Byonic, searching separately for O- and N-glycopeptides (Supporting Information File 1, Tables S1–S24), and

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• , anti-inflammatory, antimicrobial, anitubercular, psychotropic and anticancer [54][55][56][57][58][59][60]. The marketed cancer drug dasatinib [61] continues to prove its worth. In this work, it is shown that highly substituted oxazoles and aminothiazoles could be accessed directly from the reaction of

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• organ and protect the payload during the passage through physiological barriers. Most importantly, pH-sensitive DDS are considered as suitable carriers for chemotherapeutics [44][45][46]. Furthermore, peptides also play an important role as active moieties for many diseases, including cancer [47

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• of 77 with Kitahara’s sulfone 119, proceeded less efficiently (22% yield). In a subsequent assay for repressed cell proliferation against the human prostate cancer cell lines LNCaP, LNCaP95, and CWR22Rv, these authors reported IC50 values of 63, 175, and 93 nM, respectively, for 124. These can be

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• arylhydrazono-DHBERs and -THBERs has been evaluated on NCI-H1975 lung cancer cells. Keywords: antiproliferative agent; dihydroberberine; hydrazones; reduction; tetrahydroberberine; Introduction The rhizome of Coptis chinensis Franch. is a common remedy in traditional oriental medicine for the treatment of

• ]. Evaluation of the antiproliferative activity of hydrazono-DHBERs 2 and hydrazono-THBERs 3 As regards the in vitro experiments on lung cancer cells, two different tests were applied to evaluate the effects of hydrazono-DHBERs 2a–n and hydrazono-THBERs 3a–g,i–n [70] on the NCI-H1975 cell proliferation. Both

• WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt] (Figure 5) and SRB (sulforhodamine B) (Figure 6) assays revealed that DHBER significantly reduced the cancer cell proliferation as compared to untreated cells both at 24 and 48 h of incubation

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

• IV inhibitor carmegliptin (2, DPP IV) with potential for the treatment of type-II diabetes [3][4]. A comparative study on novel classes of anticancer drugs identified benzo[a]quinolizines 3 and 4 (Figure 1) to be useful for a specific inhibition of heat shock response in cancer cells, which strongly

• enhances the treatment by sensitizing cancer cells to anticancer drugs [5]. The presence of such structural pattern has driven the development of various approaches for its obtaining – based either on isolation from naturally occurring sources or through multistep synthetic routes [6]. The pyrrolo[2,1-a