Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• apoptosis at concentrations as low as 100 pM. The higher activity of 1 in comparison to 2 (Figure 1) is possibly related to the ability of 1 to interact simultaneously with adjacent baculovirus inhibitory repeat (Bir) domains in the human X chromosome that encodes IAP (inhibitor of apoptosis) [4]. In

• inhibitory activity against Bacillus subtilis in a preliminary assay. Apoptosis inducer C2-symmetric 1,3-diyne-linked peptide 1 and its inactive monomer 2. Expanded region of the ESI-MS spectrum (positive mode) and the HPLC chromatogram of the crude mixed library of 1,3-diyne peptoids (8f, 8h, 8j, 9, 10 and

Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

• Éva Rajnavölgyi,
• Renáta Laczik,
• Viktor Kun,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3152–3160, doi:10.3762/bjoc.10.332

• removal and the replenishment of cholesterol from cells treated by DHA. The methylated β-CD removes not only cholesterol but also some phospholipids from the membrane thus inhibiting the efflux function of P-glycoprotein [24][25], and at higher concentrations induces apoptosis in the rat alveolar cell

• line NR8383, in human alveolar basal epithelial lung A549 adenocarcinoma cells and in the T-cell leukemia cell Jurkat, respectively [26]. On the contrary, the methylated α-CD derivatives showed no interaction with membrane cholesterol and did not cause apoptosis in these cells [24]. The effect of

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• , lactitol efficiently controlled the apoptosis triggered by TcTS [23]. The synthesis of multivalent glycoclusters designed to be high affinity ligands for specific proteins has been an active area of research during the last years [24][25][26][27][28]. Among them, tetravalent glycoclusters bearing β

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• lead to neuronal cell death [8], and it stimulates cell division of neural cells through extracellular signal-regulated kinase (Erk) activity [9]. This process increases the ability of long-term memory and the efficiency of memory in mice [10]. Fisetin has also been found to induce apoptosis of

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• activation, cell growth, differentiation and apoptosis. Among different families of lectins, the ones showing a selectivity for β-D-galactoside and β-D-galactose-terminating oligosaccharides are called galectins and play important roles in a series of pathological events such as inflammation, fibrosis, heart

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

• -suited for studying the induction of apoptosis by our cationic titanocenes [50][51][52][53]. It is logical to study apoptosis induction, expressed as AC50 values, instead of nonspecific cytotoxicity, which is usually reported as LC50 values, because cytotoxic drugs operate by specific induction of

• 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

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• , apoptosis, angiogenesis, and B cell activation [8][9][10]. Galectin-3 has been reported to be involved in mechanisms that cluster cell surface glycoproteins [10][11], cross-link receptors [12], and form lattices and larger aggregates [13]. Structurally, galectin-3 is composed of one carbohydrate recognition

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• trans-sialidase (TcTS) [48], a virulence factor of Trypanosoma cruzi [49][50][51]. It was shown that lactitol prevented apoptosis caused by TcTS although it is rapidly eliminated from the circulatory system [52]. With the aim to improve bioavailability, PEGylation of lactose analogs was performed using

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• (Figure 1) was able to elicit in vivo antimelanoma antibodies [32]. More recently [33], we established that the multivalent presentation of this synthetic mimetic positively interferes with human melanoma cell (A375) adhesion, migration and resistance to apoptosis, showing a clear amplification of the

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• , anticancer and anti-angiogenesis activities, which are probably caused by the inhibition of threonyl-tRNA synthetase and apoptosis induction by caspase activation [1][2][3][4]. It bears several unusual structural elements like a cyclopentane ring and a carbonitrile (Figure 1a), which are built-up by

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

• Midori A. Arai,
• Kyoko Uchida,
• Samir K. Sadhu,
• Firoj Ahmed and
• Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

• inhibition of Hh- related protein expression (Figure 4). The effect of 1 on the expression of a Hh membrane receptor, PTCH, and an anti-apoptosis protein BCL2 in HaCaT cells expressing exogenous GLI1 (reporter assay cells) is shown in Figure 4A. At a concentration of 3.0 μM, physalin H (1) inhibited the

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• Biotechnology and Systems Biology, University of Kaiserslautern, Paul-Ehrlich-Straße 23, D-67663 Kaiserslautern, Germany 10.3762/bjoc.9.323 Abstract Survivin, a member of the IAP (inhibitor of apoptosis) gene family, is overexpressed in virtually all human cancers and is functionally involved in the inhibition

• of apoptosis, regulation of cell proliferation, metastasis and resistance to therapy. Because of its upregulation in malignancy, survivin has currently attracting considerable interest as a new target for anticancer therapy. In a screening of approximately 200 strains of imperfect fungi for the

• µM (1.3 µg/mL). Moreover, it also reduced mRNA levels and protein synthesis of survivin and triggered apoptosis. Keywords: apoptosis; inhibitor; natural products; secondary metabolite; structure elucidation; survivin; Introduction Survivin, a member of the inhibitor of apoptosis (IAP) protein

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• a 1,2-amino alcohol moiety at C-3 and C-4. Due to its interesting structure and biological activities, for instance cytotoxicity and apoptosis promotion of several cancer cell lines [3][4][5][6] the synthesis of this natural product attracted the attention of many research groups resulting in more

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• over-produced in cancer cells that are resistant to apoptosis-inducing chemotherapy agents, so antimycins have great potential as anticancer drugs used in combination with existing chemotherapeutics. Here we review what is known about antimycins, the regulation of the ant gene cluster and the unusual

• chemotherapeutic agents whose mode of action is to trigger apoptosis. A small molecule screen identified antimycins as potent inhibitors of Bcl-2-related proteins where they were shown to bind to the hydrophobic groove [28]. A synthetic derivative of antimycin A3, 2-methoxyantimycin A3 (Figure 1), no longer

• inhibits the respiratory chain, but still promotes apoptosis in cells over-producing Bcl-2-related proteins [29]. This suggests antimycin derivatives could be used alongside traditional apoptosis-inducing chemotherapeutics to block drug resistance and kill cancer cells [30]. Therefore, there is significant

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• -oxadiazoles are widely used in synthetic chemistry, e.g., in the search for antitumor agents. Cancer consists of more than one hundred different diseases, all of which are characterized by the uncontrolled growth and spread of abnormal cells. In this context, the identification of drugs acting as apoptosis

• inducers represents an attractive approach for the discovery of new anticancer agents. 1,2,4-oxadiazole A (Figure 2) was found to act as an apoptosis agent by a high-throughput screening (HTS) assay [8]. A series of 1,2,4-oxadiazole-5-carboxamides B have been synthesized and tested as inhibitors of the

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• inactive in the tested concentration range, although aurachin analogue 18 was determined to have a cytotoxic activity (IC50) at ca. 1 µg/mL. This might be due to differential effects on different cell lines, a different time course of electron-transport inhibition, or a different mode of inducing apoptosis

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• modulator on the CaSR (1, Figure 1) [5]. The CaSR is the main regulator of serum calcium homeostasis and plays a central role in several cellular processes such as secretion and regulation of peptide hormones (most importantly parathyroid hormone), ion-channel activity and apoptosis in certain cell types [6

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• immunity against Gram-positive bacteria. Additionally, NOD1 has been associated with the induction of NF-κB activation, caspase-1 activation and apoptosis [26][27][28]. Genetic mutations in NOD are associated with numerous inflammatory conditions, including Crohn’s disease and pancreatitis [29][30][31][32

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• Allison S. Limpert Margrith E. Mattmann Nicholas D. P. Cosford Apoptosis and Cell Death Research Program, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, United States 10.3762/bjoc.9.82 Abstract Amyotrophic lateral sclerosis (ALS) is a fatal

• , and apoptosis. However, studies using tissue samples from ALS patients report that they display elevated GSK-3 levels in the spinal cord [61]. Increased GSK-3 activity has also been reported in the motor neurons of SOD1 G93A mutant mice [62]. Using a GSK-3 inhibitor that crosses the BBB (27), Koh et

• previously determined to upregulate neuronal apoptosis inhibitory protein (NAIP/BIRC1), a cytoprotective protein that ameliorates oxidative-stress-induced cellular death [67]. Intragastric administration of 31 to SOD1 H46R mice, prior to symptom onset, was discovered to delay symptom onset as determined by

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

• .8.233 Abstract Phallotoxins inhibit the dynamics of microfilaments in cells and lead to apoptosis. Due to poor cellular uptake these effects cannot be studied in live cells, even at millimolar toxin concentrations, nor can phalloidin be used for the elimination of tumor cells. Uptake is greatly enhanced

• increasing amounts of the toxin were found in endocytotic vesicles. After 24 h most of the rhodamine-labeled toxin was still in endosomes, while some of it had found its target, as concluded from the decoration of filaments. Phalloidin causes apoptosis of cells Under the microscope, cells treated with

• membrane-permeable phalloidin derivatives appeared shrunken and developed blebs, as described for cells undergoing apoptosis. Treatment with annexin followed by flow cytometric analysis showed a fluorescence distribution typical for apoptosis and similar to that induced by camptothecin. Cells treated with

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• ) and a double conjugate (2) of (sC18)2 and Cym2 (Table 1, Scheme 1). For comparison, we also synthesized bioconjugates with known cytostatic agents: the common DNA alkylating anticancer therapeutic chlorambucil (Cbl, 3), which may induce apoptosis, and the cell impermeable proapoptotic peptide (KLAKLAK

• that it is mainly induced by necrosis, albeit apoptosis could also be demonstrated to some extent [12]. The high degree of membrane leakage even after 1 h and, thus, the rapidly occurring induction of cell death again speak in favor of mostly necrotic cell death. This is also true for compounds 3 and 4

• , which exert the same effect on cell morphology (Figure 8) and induce an equal amount of LDH release (Figure 9). This is surprising at least for compound 4, since several PAD–CPP conjugates were shown to induce apoptosis upon cytosolic delivery [28][29]. It is possible, though, that the even higher

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• cell surface receptor, belonging to the tumor-necrosis-factor receptor superfamily, which induces apoptosis. Fas-associated phosphatase-1 (FAP-1) is a Fas binding protein, which interacts with 12 to 15 of the C-terminal amino acids of the Fas receptor; however, the necessary and sufficient region for

• photoswitchable ligands. For instance, Fas-associated studies in certain cells using the tripeptide SLV suggest that this small peptide alone can induce apoptosis [14][15]. Related peptides containing class I C-terminal sequence motifs, e.g., SKV, are also derived from viral origins [16]. The latter specific

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• Smo [14][15]. Cyclopamine can effectively induce a decrease in proliferation and an increase of apoptosis in several murine models [16][17]. However, the clinical development of cyclopamine as a therapeutic in cancer is hampered by its poor aqueous solubility (ca. 5 µg/mL) and acid lability

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• ; microtubules; NHK; Introduction The discovery of compounds that function as anticancer agents by altering the dynamics of microtubules continues to be an important goal in medicinal chemistry. Such agents can force the cell to exit mitosis aberrantly, leading to apoptosis [1][2]. Important classes of

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

• Da Xu,
• Michael A. Drahl and
• Lawrence J. Williams

Beilstein J. Org. Chem. 2011, 7, 937–943, doi:10.3762/bjoc.7.104

• terrestrial plants, algae, and insect pheromones that purportedly have anticancer, antifungal, and antibiotic activity, among others. For example, parthenolide (6) has anti-inflammatory and anti-hyperalgesic effects and induces apoptosis of human acute myelogenous leukemia stem and progenitor cells [24