Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• normal lymphocytes (IC50 = 230.8 µM). Keywords: aminophosphonic derivatives; cytotoxicity; fluorescence properties; MTT test; pyrene-1-carboxaldehyde; Introduction The biological activity of aminophosphonic systems is very well known and described, in aspect of their crop protective [1], antibacterial

• cytotoxicity against both tested cancer cell lines HT29 (IC50 = 24.2 µM) as well as HCT116 (IC50 = 20.8 µM) cells, and it simultaneously was not strongly toxic for normal human lymphocytes (IC50 = 230.8 µM). However, HT29 cells were more resistant to 3Ad than HCT116 cells. Therefore, the aminophosphonate 3Ad

• showed a carcinoma-specific cytotoxicity against human colon cancer cells. A similar correlation was observed for the aminophosphonic derivative 3Ac, which was strongly cytotoxic against both colon cancer cell lines, but in contrast to 3Ad, was also toxic for lymphocytes. Paradoxally, compound 3Ac

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• indicated that the newly synthesized tricyclic flavanoids exhibit similar or even better antimicrobial properties. However, due to the lack of cytotoxicity results one may assume that the investigated structures represent a promising class of compounds. In summary, the newly synthesized compounds exhibit

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

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• essential for bacterial survival or growth and offers selectivity to strike only bacterial cells (without cytotoxicity to human cells). There are mainly four classical target processes for antibiotics: bacterial cell wall biosynthesis, bacterial protein biosynthesis, DNA replication and folate metabolism

• ). These values were comparable to those of the naturally occurring congeners of the A and B series [22]. Generally, derivatives with the naturally occurring L-configuration in the leucine moiety showed slightly better activities. These lipophilic analogues were also tested for cytotoxicity towards Hep G2

• cells and showed no cytotoxicity (IC50 > 100 μg/mL) [114]. In another series of analogues with different peptide units, the pentadecyl side chain of 91a was kept. The L-epicapreomycidine (L-epi-Cpm) unit of 91a was replaced by L-capreomycidine (L-Cpm, 92a), L-arginine (L-Arg, 92b) and L-ornithine (L-Orn

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

• focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry. Moreover, the cytotoxicity of the target compounds towards selected cancer cells is determined. Results: Introduction

• -2-azido-hexopyranoses have potential as synthons in oligosaccharide assembly. Keywords: amino sugars; cytotoxicity; fluorinated carbohydrates; fluorine; hexosamines; Introduction Derivatives of D-glucosamine (GlcN) and D-galactosamine (GalN) are essential amino sugar components of glycans in

• ][29]. Herein we also report on the cytotoxicity of prepared fluoro analogs in the human ovarian cancer A2780 and prostate cancer PC-3 cell lines. Preliminary results for the synthesis of compounds 5 and 6 were communicated earlier in a letter [30]. Results and Discussion Synthesis The synthesis

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• against L. donovani, L. infantum and L. amazonensis (promastigotes and intracellular amastigotes). The cytotoxicity of the butanol fraction in murine macrophages was found weak, with an IC50 value at 290 μg/mL. However, the butanol fraction displayed activity against L. amazonensis intracellular

• cytotoxicity against murine macrophages and the leukemic cancer cell lines. Experimental Solvents, materials and instruments Ethanol for extraction and organic solvents for partitioning (hexane, dichloromethane, ethyl acetate, and butanol) as well as for CPC were pro-analysis grade (p.a.). Water was distilled

• experiments were performed at least three independent times in triplicate. In vitro cytotoxicity against leukemic cells The cell lines used in this study were HL60 (Acute Promyelocytic Leukemia), JURKAT (Acute T cell Leukemia) and REH (Acute Lymphocytic Leukemia non-T; non-B). The cells were grown in plastic

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• like leprosy caused by M. leprae. Recently, hydnocarpin (isolated from Brucea javanica; which was named as (−)-hydnocarpin, even though the enantiomeric purity was not determined) has been described as potentiator of vincristine’s cytotoxicity due to MDR inhibition [18]. Furthermore, 5

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• inhibited 10 out of the 24 kinases tested. The results of the MTT and the kinase assay showed a similar pattern, and hence it was concluded that protein kinase inhibition should be one mechanism leading to the cytotoxicity of 17. In a study using human colon carcinoma cells to elucidate the cell death mode

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• Hergenrother and it was found to have low cytotoxicity, enter DM1 model cells, dissolved the MBNL1 foci and partially corrected the missplicing of two key pre-mRNAs, cTNT and IR. A terrific collaboration with Professor Edwin Chan’s group at the Chinese University of Hong Kong allowed the compounds to be tested

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

• inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards

• to increase water solubility, stability and bioavailability of those drugs [56][57]. In such a way, the bioavailability of genistein was found to be increased by complexation with CDs [58]. Cytotoxicity to cancer cell lines The cytotoxicity of flavanones and their inclusion complexes against three

• -loaded nanoparticles which exhibited significant cytotoxicity at high concentrations (30, 40 and 50 μg/mL) [59]. At low concentration (0.025 mM), naringenin complexed with DM-β-CD exerted a higher effect on MCF-7 and HeLa cells than free naringenin. However, for CaCo-2 cells, the effect of the naringenin

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• CuSO4·5H2O and sodium ascorbate in DMF [35][36]. All the obtained compounds were evaluated for in vitro cytotoxicity against a panel of five human cancer cell lines, where compounds 45 and 46 displayed the highest and broadest spectrum activity against all five cancer cell lines under study (Scheme 16

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

• of 1 and 2 were confirmed by an 1,1-ADEQUATE experiment. Compounds 1 and 2 showed a mild to moderate cytotoxic activities against KB-31 and FS4-LTM cell lines. Only aplysinin A (2) exhibited cytotoxicity against MCF-7 cells. Keywords: alkaloids; Aplysina lacunosa; bromotyrosine; marine natural

• luteus; Gram-negative: Peumonia aruginosa and Klebsiella pneumonia] and antifungal Candida albicans using microdilution technique. The MIC was defined as lowest concentration that shows 50% growth inhibition after 24 hour incubation. Cytotoxicity assay The cytotoxicity was determined using WST-1 cell

• ), hexadellin B (10), and diacetylhexadellin B (20). NMR data of aplysinin B (3) (600 MHz, DMSO-d6) and compound 21. Cytotoxicity of the isolated compounds (IC50).a Supporting Information Supporting Information File 448: 1D, 2D NMR, and CD spectra of three new compounds. 1D NMR, mass and CD spetra of all known

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

• preliminary result suggests that the inclusion ability of Lac-β-CyD is still maintained. Cytotoxicity of Lac-β-CyD To reveal the cytotoxicity of Lac-β-CyD, we examined the WST-1 method (Figure 3). Here, we used U18666A-treated HepG2 cells as NPC-like cells, because U18666A inhibits an intracellular

• cholesterol trafficking and has the potential to induce NPC disease phenotype [16]. No significant cytotoxicity of Lac-β-CyD was observed in U18666A-treated HepG2 cells at 1 mM for 24 h. The following studies were performed under the experimental conditions. Cellular uptake of TRITC-Lac-β-CyD To reveal

• cells, which accumulate the cholesterol and sphingolipids in cells, were prepared by the treatment with DMEM containing 1.25 μM U18666A for 48 h. Cytotoxicity In a similar manner as described in [30], cytotoxicity was assayed by the WST-1 method. Briefly, U18666A-treated HepG2 cells were seeded at 3

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

• mice fibroblasts. Only minor antimicrobial activities were obtained for citrinamines B–D (2–4) whereas no activities were found in the cytotoxicity assay for citrinamines A–D (1–4). Experimental General experimental procedures 1H, 13C, and 15N NMR spectra were conducted on Bruker Avance I 400 MHz

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• cytotoxicity against a number of tumour cell lines. Keywords: modified Claisen rearrangement; sesquiterpene; chromenol; total synthesis; Introduction The panicein family is an unusual family of natural products, which generally consist of an aromatic sesquiterpene group linked to a quinone (as seen in

• isolated in 1994 from Reniera mucosa alongside its non-cyclised isomer 1, and ten other members of the panicein family [3]. Panicein A2 (5) and D (2) were reported to exhibit in vitro cytotoxicity against four cancer cell lines (P388 mice lymphoma, A549 human lung carcinoma, HT29 human colon carcinoma and

• with the earlier report that stated 5 exhibits in vitro cytotoxicity against a number of cell lines (ED50 = 5 μg/mL). Members of the panicein family of aromatic sesquiterpenoids. Proposed biogenesis of panicein A2 (5). Retrosynthetic analysis of panicein A2 (5). Synthesis of ketone 13. Synthesis of

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro. Keywords: antimicrobial; chalcone; cholesterol; cytotoxicity; glycoside; triazole; Introduction Cholest-5-en-3β-ol (cholesterol, 1

• antifungal activities against the filamentous fungal strain Aspergillus flavus (Link) and the yeast forming fungal strain Candida albicans (ATCC 7102) were moderate compared with amphotericin B in vitro. In the cytotoxicity study, this derivative was the most cytotoxic one against the prostate cancer PC3

• cytotoxicity of a lactose scaffold with a cholesterol moiety at the C-3 carbon of the B ring of the lactose. This is because chemically modified 3β-lactosides were emerged as potential galectin-3 inhibitors. Galectin-3 is a member of the protein family known as galectins and this subfamily is believed to be

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• Dactylospongia [24] and has significantly lower cytotoxicity. The absolute configuration of the natural material is not firmly established due to discrepancies in optical rotation values between natural and synthetic samples [25]. Zampanolide and dactylolide have engendered world-wide interest from the synthetic

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

• ] that summarize their bioactivity. Herein, a synopsis of the newly published bioactivity of pyridoacridine will be provided as well as pharmacophores associated with the activity and a discussion on the evolution of the bioactivity and the structure modification. Cytotoxicity The biologically tested

• [2,3,4-kl]acridin-4-one scaffold which could be considered as the pharmacophore. The cytotoxicity of 69–76 changes depending on the substituents attached to the benzoquinone moiety (Figure 10). Furthermore, shermilamines C (28), D (77) and F (30) also represent one of the interesting anticancer alkaloids

• at C-3 (80 and 81, Figure 12) [81]. Meridine (56) has shown moderate cytotoxicity against an array of cancer lines; nevertheless, it remains a candidate for the design of new and useful anticancer candidates. Some of its reported analogues have shown interesting cytotoxicity against various cancer

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• fungal β-N-acetylhexosaminidase evaluated [28]. Similarly, dimers of sylibin (11a,b, Figure 3) and dehydrosylibin, obtained by Novozyme 435-catalyzed acylation with the divinyl esters of dodecanedioc acid, were evaluated in terms of antioxidant activity and cytotoxicity [29]. The obvious hypothesis

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• them to serve as biomaterials. Conclusion In conclusion, we designed eight conjugates by modifying two endogenous binding peptide motifs with nucleobase and glucosamine (or not) and investigated their gelation properties, biostability, and cytotoxicity. Particularly, the mixture of 5 and 8 affords a

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• monocation, dication, and dianion of substantial stability. Riccardin C (96) is a macrocyclic bis-bibenzyl entity with pharmacological properties, including antimycotic and antibacterial effects, and cytotoxicity against P-388 mouse leukaemia and KB cell lines from nasopharyngeal carcinoma. In view of these

• licheniforme. These paracyclophane derivatives exhibit potent cytotoxicity against the KB and LoVo tumor cell lines (IC50 = 2–10 μg/mL). On another occasion, Smith and co-workers have reported the synthesis of (−)-cylindrocyclophane A (156) and (−)-cylindrocyclophane F (155) [144]. The dialkenyl derivative 152

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• , arginine (Arg) and histidine (His). To investigate the effects from introducing Arg and His to dPG, the resulting polyplexes of amino acid functionalized dPG-NH2s (AAdPGs)/siRNA were evaluated regarding cytotoxicity, transfection efficiency, and cellular uptake. Among AAdPGs, an optimal vector with (1:3

• ) Arg to His ratio, showed efficient siRNA transfection with minimal cytotoxicity (cell viability ≥ 90%) in NIH 3T3 cells line. We also demonstrated that the cytotoxicity of dPG-NH2 decreased as a result of amino acid functionalization. While the incorporation of both cationic (Arg) and pH-responsive

• residues (His) are important for safe and efficient siRNA transfection, this study indicates that AAdPGs containing higher degrees of His display lower cytotoxicity and more efficient endosomal escape. Keywords: arginine; dendritic polyglycerolamine; histidine; multivalent vector; siRNA delivery

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 carbonyl group, for future SAR studies. In addition, with compounds of the non-spirocyclic type 8 and 9 good antiplasmodial activity was also seen, with 8 being the most potent (IC50 1.94 µg/mL, 5.20 µM) of the compounds tested here. In order to further assess selective cytotoxicity, the toxicity

• of 9 towards Vero cells [18] was attempted but its autofluorescence precluded a result being obtained. These spiro heterocycles, indoloazepinoindol-17-one and azepinodiindolo compounds constitute new antiplasmodial structural leads with potentially new modes of action. Modest cytotoxicity against all

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• oxidation products cause many diseases, coronary heart disease and atherosclerosis being among the most common in modern societies [8][9][10][11]. Cholesterol oxidation products have also been proven to exhibit cytotoxicity as well as apoptotic and pro-inflammatory effects [12][13]. Therefore, in-depth