Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• inhibitory [32] and cytotoxic activity. Recently, MDM2-p53 inhibitors based on an isoindolinone scaffold [33][34] have been reported. These latter results demonstrate the versatility of the isoindolinone scaffold as MDM2-p53 inhibitor and show that significant improvements in potency may be gained by modest

• from of independent experiments performed in eightplicate (MTS assay) or in triplicate (BrdU test). *P < 0.05, **P < 0.01 and ***P < 0.001 vs untreated cells. Cytotoxic effect of 6e. The cytotoxic activity of 6e was assessed in terms of both LDH release (a) and cell death (b). LDH levels are

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• towards CNS cytotoxic activity on undifferentiated SH-SY5Y neuroblastoma cells. None of the two isomeric compounds exerted cytotoxicity on this cell line (IC50 > 150 μM for both compounds), which rules out their potential CNS antitumor activity and it also suggests them as non-neurotoxic substances. On

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• acidic media were observed in the course of the described transformation. Moreover, the intermediate 6-imino-2,7-dioxabicyclo[3.2.1]octane-4,4,5-tricarbonitriles 3 had demonstrated a cytotoxic activity in various cancer cell lines [32], therefore the derived 3,4-dihydro-2H-pyrans 2 are very promising for

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• DPPH radical scavenging activity [11], and two new prenylated indole alkaloids with cytotoxic activity [12] had been isolated and identified. In an effort to isolate additional analogues that might show similar effects, a larger fermentation was undertaken. This study led to the isolation of two

• the same as that of 1. Both compounds 1 and 2 were evaluated for their cytotoxic activity using a panel of three tumor cell lines, A549 (human lung adenocarcinoma cells), HCT116 (human colon carcinoma cells), and HepG2 (human hepatoma cells). Both compounds exhibited relevant cytotoxicity. Compound 1

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• identified by signature protein domains. Finally, many RiPPs do not possess antimicrobial or cytotoxic activity, so are not identified by classical activity-based screens. Mass spectrometry (MS) represents a relatively unbiased approach to screening for the production of novel RiPPs, although this is non

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

• ), Candida albicans (DSM 1665) and Mucor hiemalis (DSM 2656, 33.3 μg mL−1 in each case). Significant cytotoxic activity was revealed for 22 towards SKOV-3 (IC50 = 2.4 μM), KB3-1 (IC50 = 5.3 μM), as well as A431 (IC50 = 8.45 μM), while 23 showed remarkable cytotoxicity against cell lines HUVEC and KB3-1 (IC50

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• cell growth creates an avenue for their use in the development of anticancer drugs, it also limits their utility as agents to modify the cellular glycome [62]. The cytotoxic activity of peracetylated monofluoro analogs 1, and 4–6, their 1-O-deacetylated derivatives 2, and 49–51, difluoro analogs 7 and

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• cytotoxic activity. They can regularly be found in improperly stored food, hence, entering the food supply chain [6]. Further coumarin derivatives, e.g., umbelliferone (4), esculetin (5), and scopoletin (6), are subject of investigation due to their pharmacological properties, i.e., anticancer effects

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• residues. Beauvericin has antibacterial, antifungal, and insecticidal activities, in addition to its potent cytotoxic activity against human cell lines [130]; attributes which indicate a crucial role in the infection process. The red 1,4-bibenzoquinone derivative oosporein (44) was first identified in the

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• , the cytotoxic activity on CaCo-2, HeLa and MCF-7 carcinoma cell lines of inclusion complexes was also determined. Results and Discussion The binding free energy of inclusion complexes between naringenin with β-CD and DM-β-CD has been previously reported by our group [40]. In the present work, we

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• activity. Aplysinin B (3) was not subjected to any biological activity test due to the minute amount and its existence as the minor compound of a mixture. The results showed that 1 and 2 exhibited mild cytotoxic activity against KB-31 epidermoid carcinoma cells (IC50 = 69 and 26 µM, respectively). Only 2

Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• found to possess respiratory stimulating effects [12], N-substituted putrescine and cadaverine have shown antiproliferative and cytotoxic activity [13][14], N-decyl and N-dodecyl derivatives of putrescine, N-(p-tolyl) derivatives of cadaverine and hexane-1,6-diamine have demonstrated affinity to NMDA

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• with Scheffe's test. The level of statistical significance was set at p < 0.05. Preparation scheme of Lac-β-CyD. MALDI–TOF MS (A) and 1H NMR (B) spectra of Lac-β-CyD. Cytotoxic activity of β-CyDs in U18666A-treated HepG2 cells after treatment for 24 h. U18666A-treated HepG2 cells were incubated with

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• cytotoxic activity. Classical agar diffusion assays were performed using the fungus Aspergillus niger, the yeast Saccharomyces cerevisiae as well as the Gram-negative bacterium Escherichia coli, and the Gram-positive bacterium Micrococcus luteus and Mycobacterium phlei as test organisms. In agar diffusion

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• hydroquinoline derivative 327 in 81% yield. Further, they have used the bicyclic compound 327 as a key building block in the total synthesis of (+)-luciduline (Scheme 71). Lepadins are natural products consisting of cis-fused decahydroquinoline subunits and they display cytotoxic activity against many human

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• synthetic compounds, has been widely investigated. Many of them displayed cytotoxic activity in addition to other bioactivities such as antiviral, antifungal, antibacterial, antitumor and antiparasitic potential [41]. Several reviews on pyridoacridine alkaloids have been published between 1983–2015 [35][43

• pyridoacridines interestingly displayed strong (IC50 < 10 µM) cytotoxic activity in vitro. For instance, pantherinine (69) isolated from Aplidium pantherinum [77] and cystodytins A–G (70–76) from Cystodytes dellechiajei [36][78] are all potent anticancer metabolites. Their structures are based on a 4H-pyrido

• cell lines [57][69]. As shown in Figure 13, the cytotoxic activity slightly improves when the OH group of the E ring of 56 is oxidized to afford 82 [82]. This bioactivity significantly increases with more selectivity without any substituent on the 8H-benzo[b]pyrido[4,3,2-de][1,7]phenanthrolin-8-one

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• recognized as active agents against tuberculosis and malaria [3][7], cardiovascular diseases [3], and cancer [4]. Cinnamates show depigmenting [4], antidiabetic, antihyperglycemic, anticholesterolemic, anti-inflammatory, hepatoprotective, CNS depressant, anxiolytic, and cytotoxic activity [7]. Cinnamate

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• the development of major mycobacterial resistance [19]. Patchy cytotoxic activity was seen with the N-substituted isatins 32, 33, and 34. Compounds of this general type, but incorporating N-arylmethyl as well as 5,7-dibromo substituents, have given rise to potent anticancer compounds with activity

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

• with IC50 values of 34.77–45.68 μM. Keywords: cytotoxic activity; neolignans; Trogopterus xanthipes; Introduction Chemical studies of natural products including ones derived from plants and microorganisms have led to the isolation of numerous novel metabolites with biological activities [1][2]. As a

• controlling of antithrombin levels, inhibition of platelet aggregation, cytotoxic activity, immunity enhancement, and anti-inflammatory activities. Isolation of compounds from the methanol extract of Trogopterus feces was presented before by our group [12]. In the present investigation, chemical evaluation of

• of 34.77–45.68 μM using adriamycin as a positive control (IC50 = 0.18 μM). Additionally, compound 1 showed very weak cytotoxic activity against MCF-7 cells with an IC50 of 94.69 μM. None of the compounds affected the HeLa cells. Conclusion In summary, two novel neoligans (trogopterins A and B) and a

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• combined with moieties covalently interacting with DNA and RNA. One of the most promising examples reported recently revealed that in a series of mono functional, cationic platinum(II) compounds, phenanthriplatin displayed a greater cytotoxic activity than either cisplatin or oxaliplatin despite a fact

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

• desposit@ccdc.cam.ac.uk. Biological assays Cytotoxic activity against 11 human cancer cell lines, K562 myeloid leukemia, SH-SY5Y beuroblastoma, SGC-7901 gastric adenocarcinoma, HepG2, SMMC-7721 hepatocellular carcinoma, A549 lung cancer, MCF-7, MDA-MB-231 breast cancer, HCT116, SW480 colon cancer, HT29

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• these compounds is of particular interest as 2-prenyltryptophan derivatives have been obtained or isolated from a diverse array of natural sources [66][67] and, in general, prenylation at the indole ring leads to a significant increase in the antioxidant and/or cytotoxic activity of tryptophan

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• a tetrasubstituted trans-cyclopropane subunit. The compound shows modest cytotoxic activity against murine melanoma cells [98][99]. The first enantioselective total synthesis of anthoplalone was achieved by Hanessian and co-workers and utilized their chloroallyl phosphonamide anion cyclopropanation

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

• our cationic carbonyl-substituted titanocenes. Comparison of the three most active complexes also allows the identification of structural features essential for cytotoxic activity. First, a bulky substitution of the cyclopentadienyl ligand is favorable. Second, positioning of the triazol in close

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• ][8] and display both antibiotic and cytotoxic activity [9]. They have a polycyclic xanthone aglycone in common, which is glycosylated at the C14–OH group. In Figure 1 the structure of kigamicin B, which carries a D-amicetose disaccharide unit, is shown as a representative example. Another antitumor