C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• can interact with intracellular targets to induce cytotoxicity [28][29][30][31][32]. Several functionalities have been inserted as linkers on the 2’-oxa-3’-aza-4’a-carbanucleoside skeleton in order to confer novel mechanisms of action for nucleoside mimics: in this context, the 1,2,3-triazole unit

• different biological effect with respect to 2’-oxa-3’-aza-4’a-carbanucleosides devoid of the triazole unit, such as compounds 2 and 8, which are endowed with antiviral activity, but do not show any cytotoxicity The ability of compounds 13a–g and 14a–g to interfere with the replication of different DNA and

• maintenance medium (DMEM with 2% heat inactivated FCS) was used to culture the viruses. Cell viability. The cytotoxicity of the tested compounds was evaluated by measuring the effect created on cell morphology and/or cell growth (cytostatic activity). Cell monolayers were prepared in 24-well tissue culture

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• -methylkaempferol exhibits modest cytotoxicity [17]. These methylated derivatives of flavonols are found as natural products in relative low quantity, whereas kaempferol is relatively rich in plants. Therefore, it is quite worthwhile to develop procedures for the preparation of methylated derivatives of kaempferol

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• of the therapy. Another major factor is that anticancer drugs have a wide distribution capacity in the body and owing to non-selective cytotoxicity of these drugs not only the cancer cells but also healthy cells are killed. Due to low therapeutic indices of anticancer drugs, a rapid increase and

• cell line by the USP to test toxicity of polymeric systems and thus used in this study to investigate whether the toxicity of nanocapsules is associated with the polymer material itself or not. Therefore cytotoxicity of blank anionic and cationic CD nanocapsules was evaluated against L929 cells with an

• nanocapsules, physicochemical characterization of CPT-loaded CD nanocapsules, determination of CPT loading, in vitro CPT release studies, CPT stability in simulated GI fluids and cytotoxicity, anticancer efficacy and permeability assay of CD nanocapsules. Supporting Information File 140: Experimental data

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

• structures as well as simple Ugi products exhibit promising biological profiles, e.g., cytotoxicity [13][19][20], fungicidal [21][22] and antibacterial properties [23][24][25][26], or inhibition of histone deacetylases [27]. The Ugi post-modification strategy has also been employed in the synthesis of

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• rings) are unexpected, novel, secondary metabolites, isolated from the marine-derived fungus Aspergillus ostianus strain 01F313 in bromine-modified 1/2PD culture medium [1][2][3][4]. Interestingly, these compounds show cytotoxicity against mouse lymphocytic leukemia cells (L1210) with LD50 values of 2.1

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• temperatures [47][48][49]. Only the CD-HES conjugate 6 did not show any precipitation below 100 °C which was attributed to the much higher hydrophilicity of the anionic carboxylate groups at the HES backbone compared to unmodified HES. Cytotoxicity assays The effect of the CD polymer 5a on the cell viability

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• new phenolic compound (trogopterin C) were isolated from the crude methanol extract of Trogopterus feces for the first time. The absolute configurations of compounds 1, 2, and 4 were determined by comparing CD spectra and optical rotations. The levels of cytotoxicity against three tumor cell lines (HL

• ', C-2', and C-6'; H-9b→C-1, C-7, C-8, C-1', C-2', and C-6'; H-2'→C-9, C-3', C-4', and C-6'; H-4'→C-2', and C-6'; H-5'→C-1' and C-3', H-6'→C-9, C-2', and C-4'; HREIMS (m/z): calcd for C15H16O3, 244.1099; found, 244.1105. Assessment of cytotoxicity Different types of cancer cells (HL-60, HeLa, and MCF-7

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• (SBECD)) for the formation of inclusion complexes. HPBCD and SBECD showed low cell cytotoxicity in human keratocytes as assessed by the label-free xCELLigence system for real-time monitoring. The fluconazole–HPBCD complex was incorporated into an ion-sensitive ophthalmic gel composed of the natural

• measurement. As shown in Figure 3c, HPBCD induces cytotoxicity immediately after its administration, reaching an initial IC50 value of 40 mg/mL. Subsequently, its value decreases quickly during the exposure period and reaches a stable value of 16 mg/mL after 2.5 hours, which is maintained for over 15 hours

• . This result shows that the cytotoxicity of HPBCD is enhanced with increasing exposure time. In the case of SBECD, cytotoxicity was observed immediately after its addition, reaching an initial IC50 of 22 mg/mL, which is slightly lower than the initial data observed for HPBCD. It then increases gradually

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• Information File 1. In vitro antiprotozoal activity assays: The in vitro activities against the protozoan parasites L. donovani and P. falciparum as well as cytotoxicity assessments against L6 cells were determined as reported elsewhere [58]. The following strains, parasite forms and positive controls were

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• intermediate 2 undergoes decarboxylation to form 3 through Baeyer–Villiger oxidation to form the 7-membered lactone 4, then hydrolyzation, decarboxylation and lactonization to finally give aspergiloid I (1). Aspergiloid I (1) was evaluated for its cytotoxicity against eleven human cancer cell lines, K562

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• investigate the cell compatibility of the conjugates, we incubated compounds 1–8 with HeLa cells [37] for 3 days at a concentration range from 20 μM to 500 μM. We compared the cytotoxicity of conjugates 1, 2, 5, and 6 in Figure 2. Compounds 5 and 6 serve as the control for compounds 1 and 2 since they do not

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• ; DNA methyltransferase; nucleic acids; oligodeoxynucleotide; thionucleoside; Introduction Covalent interstrand DNA cross-links have long sparked clinical and biochemical interest. The cytotoxicity of bisfunctional alkylating agents like nitrogen mustards or chloroethyl nitrosourea (CENU) derivatives

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• applications are also supported by the preliminary bioactivity screening of the AP-series, which revealed low cytotoxicity toward human cell lines. Experimental General 7,16-Bis[2-(3-bromopropoxy)benzoyl]-5,14-dihydrodibenzo[b,i][1,4,8,11]tetraazacyclotetradecine, 7,16-Bis[2-hydroxybenzoyl]-5,14-dihydrodibenzo

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• cytotoxicity of 1 raised concerns about potential food intoxication. To evaluate the presence of 1 in these products, extracts were prepared and examined by antifungal testing and LC–MS analysis. The products were softened or desalted by soaking in water and then subjected to the same extraction and

• cyanobacterium A. sacrum for the first time. A. sacrum is endemic to the Aso water system in Japan. As a result, we discovered a new oxylipin-derived macrolide 1 with a broad antimicrobial spectrum and cytotoxicity. Although the safety of this alga as food is secured by 250 years of consumption as a premium

• inhibitory concentration (MIC). Cytotoxicity testing and cell morphology observation The cytotoxicity against 3Y1-B clone 1-6 rat fibroblasts and the action of sacrolide A (1) on the morphology of the same cell line were evaluated by the procedures described in [22]. Method to precook raw alga for the

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• ], exhibits significant cytotoxicity in vitro against several human cell lines such as leukaemia (CCRF-CEM, IC50 0.4 µg/mL), colon tumour (HCT-116, IC50 0.9 µg/mL), and breast tumour cells (MCF-7, IC50 0.2 µg/mL) [13]. Furthermore, such 2′-C-branched ribonucleosides are also potential agonists for adenosine

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

• active complexes allows the identification of structural features essential for biological activity. Keywords: azides; click-chemistry; cycloadditions; cytotoxicity; titanocenes; Introduction Group 4 metallocenes and derivatives of Cp2TiCl2, in particular, continue to be in the focus of contemporary

• perspectives for the immobilization of titanocene complexes. Cytotoxicity studies One of the pertinent features of titanocenes is their cytotoxicity [1][2][3][4][5]. Therefore, we investigated this particular property of our novel complexes. To guarantee comparability with a previous study [26] we discuss our

• -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

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• Center for Infection Research (HZI), and was based on the microdilution test, using 96-well micro titration plates. The MIC was defined as 50% growth inhibition after 24 hour incubation compared to that in the growth control well. Cytotoxic assay The cytotoxicity was determined using WST-1 assays

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

• phenyl group of malevamide D was also functionalized with a photoreactive diazirine moiety, which was carried through seven reaction steps. Comprehensive assessment of the cytotoxicity in a panel of 42 human cancer cell lines revealed a geomean IC70 value of 1.5 nM (IC50 0.7 nM) for malevamide D, whereas

• the photoreactive derivative proved to be less active by a factor of at least 200. COMPARE analysis indicated tubulin interaction as likely mode of action of malevamide D. Keywords: cytotoxicity; diazirines; dolastatin analogs; marine natural products; peptides; total synthesis; Introduction The

• depsipeptide malevamide D (1, Figure 1) belongs to the dolastatin class of marine natural products and has been isolated from the cyanobacterium Symploca hydnoides by Scheuer and co-workers in 2002 (7.5 mg, 0.014% of the dry weight) [1]. Malevamide D (1) was reported to exhibit in vitro cytotoxicity in the

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• determined in the agar plate diffusion assay as described previously [12]. Cytotoxicity was assayed as described previously [13]. The cell line HelaS3 was grown in DMEM medium (Invitrogen). The medium was supplemented with 10% heat-inactivated fetal calf serum (Invitrogen), 65 mg/L of penicillin G and 100 mg

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

• , and exhibited cytotoxicity against cancer cell lines with an aberrant activation of Hh signaling. Compound 1 inhibited the production of the Hh-related proteins patched (PTCH) and BCL2. Analysis of the structures of different physalins showed that the left part of the physalins was important for Hh

• in many cancers. In this study, we report the isolation of four physalins (1–4) along with the previously reported Hh inhibitors 5 and 6. In addition, we evaluated the Hh inhibitory activity by assessing the cytotoxicity against cancer cells and the expression of Hh-related proteins. Physalin H (1

• previously described method [18]. Detection of the Hh inhibitory activity was based on the decrease in the luminescence value due to reduced luciferase expression by GLI1 compared to that of the control (DMSO). In addition we always checked the cytotoxicity of the compounds against the assay cells, because a

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

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

• with or without test compounds. Luciferase activity was measured 24 h after induction using the Dual-Glo luciferase assay system (Promega, Mannheim, Germany) according to the manufacturer´s instructions with a luminometer. Cell viability testing The cytotoxicity of the compound was determined after 48

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

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• this contribution, we demonstrate that this combination can be advantageously used for the synthesis of decanolides. These natural products share a ten-membered lactone structure and are normally isolated from fungi. Diverse bioactivities have been reported, such as phytotoxicity, cytotoxicity

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

• , both derivatives induced cytotoxicity in the concentration range tested. Very subtle changes of the conformation of the piperidine ring significantly change bioactivity: While 25-epi-exo-cyclopamine 5 shows reduced activity in comparison to exo-cyclopamine 2, bis-exo-cyclopamine 6 is the most active