5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• ). Interestingly, high yields of the corresponding pyrazolo[3,4-b]pyridines 34 were obtained when reactions were carried under solvent-free microwave irradiation. The synthesized pyrazolo[3,4-b]pyridines have shown potential cytotoxic activity against cervical HeLa and prostate DU 205 cancer cell lines. A similar

• screened for their cytotoxic activity against human colon carcinoma (Colo-205) cell lines (Scheme 35). Buriol et al. [92] described the reaction of 5-aminopyrazole 16 with 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones 129 to yield pyrazolo[1,5-a]pyrimidine derivatives 130 in acetic acid and ethanol using

• (pyridin-3-yl)methanone (piperazinyl derivatives, 135) with 134 which were evaluated for their cytotoxic potential against MCF-7, HeLa, IMR 32 and SiHa cancer cell lines. Pyrazolo[1,5-a]pyrimidinyl amide derivatives 136 having piperazinyl derivatives, R1 = H, R2 = F and OCH3, R3 = H and OCH3, respectively

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• natural product is 6-nonyl-2H-pyran-2-one. The antimicrobial and cytotoxic effects of the synthetic volatiles are also reported. Keywords: enantioselective synthesis; gas chromatography; mass spectrometry; natural products; volatiles; Introduction A large variety of volatile organic compounds from

• products so far. Biological characterisation of compounds Three of the volatile metabolites identified from D. clavata (compounds 9, 14 and 17) were evaluated for antimicrobial and cytotoxic activities using a standard panel of fungi and bacteria, as well as the murine cell line L929 (Table 3). The 2

• -pyrone 17 exhibited a moderate antifungal and weak antibacterial effect, while the lactone 9 was moderately cytotoxic, but devoid of significant antimicrobial activity. The chlorinated aromatic compound 14 only weakly inhibited the sensitive test organisms Chromobacterium violaceum and Mucor hiemalis

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• ulcerans, which exhibit cytotoxic, immunosuppressive and analgesic properties. As the virulence factor of M. ulcerans, mycolactones are central to the pathogenesis of the neglected disease Buruli ulcer, a chronic and debilitating medical condition characterized by necrotic skin ulcers. Due to their complex

• and mechanisms of action Although Buruli ulcer is associated with extensive fat cell necrosis at the sites of infection, the ulcers are typically accompanied by minimal pain or inflammatory response. These macroscopic observations reflect the cytotoxic [32], immunosuppressive [35][77] and analgesic

• might be crucial for Buruli ulcer pathogenesis [35][81]. With increasing concentrations, the cytotoxic effects of mycolactone become more prominent. These are typically accompanied by a profound structural change in the cytoskeleton followed by cell cycle arrest in the G0/G1 phase. Ultimately, cell

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• methylation protocol, we explored diazomethane, but no conversion was observed at all. Finally, all of the synthesized alkaloids were tested for their cytotoxic potential in a MTT assay on the HL-60 cell line. Except for menisporphine (2) and bianfugecine (6, both IC50 values > 50 µM), all of the described

• oxoisoaporphine alkaloids and the isomers 18 and 19 showed significant cytotoxic activity. IC50 values of alkaloid 3 and of compounds 18 and 19 are ranging from 3–6 µM. Very strong cytotoxicity was determined for 6-O-demethylmenisporphine (4) with an IC50 value of 0.06 µM and for dauriporphinoline (5) with 0.23

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• active construct 6 from the liposomes. Further tests are necessary to confirm this hypothesis. Conclusion In summary, in order to develop a drug delivery system for potential theranostic applications, we prepared a submicron liposome-based formulation of a cytotoxic agent, sesquiterpene lactone

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• 2 and 3 was observed and verified and the possible reaction path and mechanism were proposed by theoretical computations. The antifungal and cytotoxic activities of 1–6 were evaluated and suggested that 2,3-dehydrogenation results in the loss of the activities and supported that the OH-α is

• findings suggested that these cycloheximide derivatives possibly exert the antifungal and cytotoxic activities via a similar mode of action. Conclusion Three new (1–3) and three known (4–6) cycloheximide congeners were obtained from the cultures of Streptomyces sp. SC0581. The structure elucidation of the

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

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• (±)-oxomaritidine (gas–liquid–solid reaction) Baxendale et al. have developed a multistep synthesis for (±)-oxomaritidine, a cytotoxic alkaloid of the amaryllidaceae family of natural products [9] (Scheme 4). The process involved seven reaction steps out of which the first two reactions were carried out in parallel

Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee

• Kalliopi Sofou,
• Demosthenis Isaakidis,
• Apostolos Spyros,
• Anita Büttner,
• Athanassios Giannis and
• Haralambos E. Katerinopoulos

Beilstein J. Org. Chem. 2017, 13, 952–959, doi:10.3762/bjoc.13.96

• -α and IFN-γ-stimulated chemokine production [48]. Costic acid exhibited selective cytotoxic effects to Spodoptera littoralis-derived Sf9 cells [49]. In spite of the diversity in biological activity, however, no acaricidal activity of either costic acid or D. viscosa extracts against V. destructor

• ) was measured according to the test protocol. Costic acid was not cytotoxic at concentrations of up to 230 micromolar (μM). Mortality of V. destructor (number of mites) after 12 h treatment with 20, 60, or 100 μL dose of acaricide. The number in parenthesis indicates the microliters of solution used in

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• stereoselective synthesis of (1R,3E,7E,11S,12S)-3,7,18-dolabellatriene, a bicyclic diterpene (Scheme 2). Dollabellanes derive mostly from marine organisms and display bioactivities such as antiviral and cytotoxic effects [59]. Dolabellatriene from a reprogrammed CotB2 contribute with antimicrobial activity

• process generally involves selection of the carbon source, media composition and in situ or post-fermentational product removal. Some terpene products have cytotoxic effects against the production host and separation from the cells is recommended already during fermentation. Ajikumar et al. also reported

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• treating asthma and post-stroke patients [16]. 1,2,4-Triazolo[1,5-a]pyridines show antifungal [17], antitumor [18], and cytotoxic [19] activities. Both types of heterocyclic cores are readily available from N-aminopyridium salts and related pyridinium-N-imines via 1,3-cycloaddition reaction [20] or

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• domains and an attenuated phospholipid condensation effect was found. These properties, which depend on the molecular position of the hydroxy group, were correlated with cytotoxic effects of the respective molecules [22][23]. In the current study, the influence of hydroxycholesterols on membrane

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• being excited with visible light, the PS – while reverting to the ground state – transfers the energy of its lowest excited triplet state to nearby molecular oxygen. This leads to an in situ generation of singlet oxygen (1O2), which is the main responsible species for cytotoxic reactions in cells [6

• systems in combined phototherapies. This approach has recently led to self-assembled systems based on a porphyrin–β-CD conjugate and a tailored nitric oxide photoreleaser forming a strong inclusion complex with the β-CD cavity [9]. This supramolecular nanoassembly simultaneously releases cytotoxic 1O2 and

• nitric oxide under illumination with visible light, resulting in amplified cancer-cell mortality [9]. By attaching porphyrin to γ-CD and dimeric β-CD, which are both able to form inclusion complexes with cytotoxic drug molecules such as doxorubicin and paclitaxel, nanocarriers with multimodal therapeutic

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• the synthesis of kinamycin 9 derivatives, which exhibited a strong cytotoxic and anticancer activity (Scheme 4) [15]. Propionic acid derivatives are also useful substrates in syntheses of 1-indanones and isocoumarins [16]. These latter are essential reagents for the synthesis of bioactive compounds

• keto-oximes 179 and 2-amino derivatives 180 are β2-adrenergic agonists tested for bronchodilating activity. The pterosin family are sesquiterpenoids naturally occurring in bracken fern (Pteridium aquilinum), some of them exhibit antibacterial and cytotoxic activity. A practical synthesis of pterosin A

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• . However, none of them showed significant antiviral or cytotoxic activities. The absence of biological activity may be attributed to various factors, such as inability to enter cells or to behave as substrates for intracellular enzymes catalyzing phosphorylation, as well as a lack of inhibition of viral

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• calorimetry (DSC). The prepared compounds were also screened for their cytotoxic activity against five cell lines. It was observed that the lipoconjugates of caffeic acid, sinapic acid, ferulic acid, and coumaric acid displayed anticancer and anti-oxidant properties. The anticancer properties of these

• due to different media used for the assays; the DPPH assay is conducted in a polar medium but the linoleic acid oxidation study is conducted in a non-polar environment. Cytotoxic activity As there were studies reported on the cytotoxicity of phenolic lipids, we have further screened the prepared

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

• -benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9–22 μM. Biological tests suggest that the antitumor activity could

• 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

• . Assessment of cell proliferation was also performed cytofluorimetrically by the BrdU assay, [48] obtaining results that reflect data from MTS test (Figure 7b). Cytotoxic effect The cytotoxic effect induced by 6a–f was evaluated by an LDH assay [49], revealing that significant cytotoxicity was exerted only at

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• diptoindonesin G, a potent cytotoxic and immunosuppressant agent [16][17], by using a highly efficient domino cyclodehydration/intramolecular Friedel–Crafts acylation/regioselective demethylation sequence as a key transformation. Very recently, a dual functional role of diptoindonesin G in modulating α and β

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• Ulrike Kauscher Bart Jan Ravoo Organic Chemistry Institute and Center for Soft Nanoscience, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany 10.3762/bjoc.12.248 Abstract Photoreactive squaraines produce cytotoxic oxygen species under irradiation and have

• interference of the PS with the triplet ground state of oxygen, leading to the production of singlet oxygen. In both mechanisms, the PS harvests the energy of incident light to form reactive oxygen species or singlet oxygen, which are highly cytotoxic [6][7]. Most clinically used PSs are based on porphyrins

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

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin, an important biopolymer that protects against a broad range of cytotoxic insults, including UV and oxidative damage [11]. While amyloid morphologies and events which induce amyloid formation are

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• mechanism is operative [31]. Indole metabolite In 1996, during a screening program for biologically active metabolites from marine ascidians, Riguera et al. identified a small group of amino acid containing compounds in a cytotoxic extract of the ascidian Leptoclinides dubius [32]. Among these compounds was

• B (8). Minosaminomycin (9) and related antibiotic kasugamycin (10). Enduracididine-containing compound 11 identified in a cytotoxic extract of Leptoclinides dubius [32]. Mannopeptimycins α–ε (12–16). Regions of the mannopeptimycin structure investigated in structure–activity relationship

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• ’-spiropyrrolidinyloxindole core show various biological effects such as bactericidal and fungicidal [21], anticancer [22], cytotoxic to MCF-7 and HepG2 cells [23][24], and advanced glycation end (AGE) product formation inhibitory activities [25] (Figure 1). Over the last decade, a lot of publications have been devoted to

• class of promising bioactive polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties. Investigations of cytotoxic activities of the synthesized products against A549, HCT116, RD, and MCF7 cell lines are in progress. Bioactive 2,3

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• monensin A, another well-known ionophore antibiotic, applying an oxidative cyclization approach using potassium permanganate [64]. Amphidinolide F Amphidinolide F (24) is a marine natural product isolated from the dinoflagellate Amphidinium sp. in 1991 [65]. The macrocyclic core of these highly cytotoxic

• advantage of the meso-geometry of the central THF diol moiety [80]. cis-Sylvaticin cis-Sylvaticin (40), a non-adjacent bis-THF acetogenin [92] (Scheme 10), was discovered in dried fruits of Rollinia sylvatica [93] and leafs of Rollinia mucosa [94]. It has been shown to be cytotoxic against several cancer

• oxide (79) in a further few steps. Teurilene Teurilene (82) is a squalene-derived cytotoxic polyether which was originally extracted from the red algae Laurencia obtusa by Suzuki et al. [138][139]. Though it is CS-symmetric, it is structurally closely related to pentacyclic C2-symmetric glabrescol [140

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