Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• corresponding chiral products 26 in moderate to excellent yields (58–99%) and good to high enantioselectivities (81–97% ee), as illustrated in Scheme 8 [40]. A preliminary evaluation on the cytotoxicity of some selected products revealed that two of them exhibited moderate to strong cytotoxicity to A549, 786-0

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• cryptophycin analogues. The O-methyl group of the unit B D-tyrosine analogue was replaced by an O-(allyloxyethyl) moiety, an O-(hydroxyethyl) group, or an O-(((azidoethoxy)ethoxy)ethoyxethyl) substituent. While the former two maintain cytotoxicity in the subnanomolar range, the attachment of the triethylene

• [2][3]. Their high cytotoxicity prompted manifold studies that were initially focussed on the total synthesis and structure–activity relationships [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. This work resulted in the identification of cryptophycin-52, a highly biologically active

• human cervix carcinoma cell line KB-3-1 (Table 1). The cryptophycin analogue 22 showed a dramatic loss of activity compared to cryptophycin-52 (2), while analogues 23 and 24 showed a reduced cytotoxicity although their IC50 values are still in the low nanomolar range. The observed dramatic loss of

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• affinity, sequence specificity, more cytotoxicity and minimizing the unwanted physiological side effects [43]. It has been observed that drugs with high degree of sequence specific binding affinity and selective alkylation of DNA could inhibit the binding of the regulatory proteins to DNA. Several

• also replaced by various amidine-like groups, such as cyanoamidine, N-methylamidine, N,N-dimethylamidine, and guanidino moieties either to increase the stability, cytotoxicity and enhance solubility at physiological pH. Comparable cytotoxicity was observed in these cases suggesting a general behavior

• anticancer drug due to its improved cytotoxicity/myelotoxicity ratio [47][48]. Brostacillin acts as an effective DNA alkylator only in presence of high levels of cellular thiols such as glutathione [49]. Moreover, it was thirty-fold more active in comparison to TAM in inducing apoptosis in A2780 human

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• receptor-mediated transcytosis after binding to LRP-1 and consequently it is often used as drug delivery vehicle, while paclitaxel bears cytotoxicity against glioblastoma. It has been shown that the brain uptake of ANG1005 was 4.5-fold higher compared to paclitaxel and the cytotoxicity remained higher in

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• The chemostability of cyclic NGR peptide–drug conjugates was studied under the treatment conditions used for the in vitro cytotoxicity experiments. Samples were taken at 0 min, 6 h and 72 h. The deamidation rate was evaluated by HPLC–MS. In contrast to the control conjugate (K) that showed high

• (HPLC), followed by 3 × 15 min centrifugation at 13000 rpm. The last step is the washing with eluent B (HPLC) 1 × 15 min, followed by lyophilization and concentration of the samples. In vitro cytostatic effect and cytotoxicity HT-1080 was maintained in DMEM while HT-29 cells in RPMI (Sigma-Aldrich

• cells. For the measurements of cytostatic effect, drug containing medium was gently removed from the plates after 6 h incubation, fresh medium was added to each wells, and the plates were further incubated for additional 66 h (72 h in total). In the case of cytotoxicity measurements, the drug containing

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• endothelial cells and RSV with low cytotoxicity towards Huh-7, HEp-2 and MT4 cells. Moreover, the triphosphate of 4 selectively inhibits, HCV RdRp and RSV RdRp over human RNA Pol II and DNA polymerases (α, β, γ) [65]. The 2'-Me compound 7 as its triphosphate (TP) shows anti-HCV activity in replicon assays [77

• imparting high potency but also high cytotoxicity [72]. A further modification to the imidazo[2,1-f][1,2,4]triazine C-nucleoside scaffold was reported by Dang et al., wherein they synthesized a series of 2'-β-Me analogues possessing a 1',2' cyclopentyl ring (Figure 9) [73]. A representative synthesis

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• of cytotoxicity, structure–activity relationships and electrochemical behaviour [95]. Derivatives that contain an aromatic amine and salicylaldehyde or 2-pyridinecarboxaldehyde moieties were found to be the most active against the HL-60 (promyelocytic leukaemia) cell line. Zhou et al. obtained

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• lines, the cyclo[DKP-isoDGR]-α-amanitin conjugates bearing the lysosomally cleavable Val-Ala linker were found to be slightly more potent than α-amanitin. Apparently, for all these α-amanitin conjugates there is no correlation between the cytotoxicity and the expression of αVβ3 integrin. To determine

• whether the increased cytotoxicity of the cyclo[DKP-isoDGR]-α-amanitin conjugates is governed by an integrin-mediated binding and internalization process, competition experiments were carried out in which the conjugates were tested with U87 (αVβ3+, αVβ5+, αVβ6−, α5β1+) and MDA-MB-468 (αVβ3−, αVβ5+, αVβ6

• is responsible for the transcription of DNA to mRNA [1][2]. Despite this strong inhibitory activity, α-amanitin exhibits only a micromolar cytotoxicity and low cellular uptake in most mammalian cells, due to its strong polarity and poor membrane permeability [2]. One notable exception are human

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• arylation reactions in synthetic organic chemistry, but their biological properties are not fully understood. Herein, after initially investigating 18 fluoro-functionalized reagents, we discovered that the ortho-fluoro-functionalized diaryliodonium salt reagents showed remarkable cytotoxicity in vitro

• )phenyl)iodonium exhibited the greatest potency in vitro against U937 cells. Evaluation of the cytotoxicity of selected phenylaryl-λ3-iodonium salts against AGLCL (a normal human B cell line) was also examined. Keywords: biological activity; diaryliodonium salt; fluorine; hypervalent iodine; lymphoma

• blood monocytes. This cell line was chosen due to the convenience with which it can be handled and its ease of growth [27]. Initially, 19 compounds [20][21][22][59][60][61][62][63][64] were examined for their potential cytotoxicity, and some of them showed potency, in particular ortho-fluoro

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

• -aminopyrazole (R = H, 16) was condensed with 38. It was attributed to cyclocondensation between 1-NH (5-aminopyrazole) and the carbonyl carbon of the enaminone. The compounds were found to have cytotoxicity against the normal fibroblast (BHK) cell line and antitumor activity against the colon cancer cell line

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• interaction with the NS5A protein. This fluorinated peptide isostere showed activity in the picomolar range against one genotype and did not exhibit any cytotoxicity (Figure 4). Pannecoucke and co-workers synthesized three heptapeptides, Gly-Gly-ψ[(Z)-CF=CH]-Phe-Ser-Phe-Arg-Phe-NH2, Gly-ψ[(Z)-CF=CH]-Gly-Phe

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• -keto-22,23-diols was synthesized and assessed for biological activities in non-plant models. Some of the studied compounds showed a marked cytotoxicity against human cancer cell lines MCF-7 and LNCaP [11][12][13]. We tested two approaches for the transformation of epicastasterone (1) and

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• into cancer cells and kills them by reactive oxygen species with cytotoxicity generated by light irradiation [94][95]. In addition to reducing the psychological burden of the patients because this process does not require surgical operation, damage to normal cells can be minimized by irradiating the

• deoxyribonucleoside conjugates. An in vitro investigation showed that cyclodextrin-linked TFEO-Pcs were ideal PDT drugs that exhibits high cytotoxicity under light irradiation while displaying little cytotoxicity in the dark (Table 2). On the other hand, interestingly, the fluorine-free tert-butylated derivative

• showed cytotoxicity even in the dark. This result suggests that the trifluoroethoxy group reduces the cytotoxicity of the phthalocyanine. Subsequently, an in vivo investigation was also conducted. Chicken embryos transplanted with cancer cells were treated with PDT by a cyclodextrin conjugate and proved

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• have been widely reported for the preparation of nanocomposites with a great range of applications, due to their low cytotoxicity and notable biocompatibility and stability [33][34][35][36][37], their catalytic application is still lacking. In addition, these natural products are easily and

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

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

• cytotoxicity against the HL-60 tumor cell line. Keywords: directed ortho/remote metalation; Eaton’s reagent; isoquinolines; Suzuki cross-coupling; Introduction Benzylisoquinoline alkaloids represent a very large group of plant secondary metabolites, which includes about 2,500 known structures. Besides simple

• , and is of considerable pharmacological interest due to the significant cytotoxicity of numerous representatives [3]. A unique subclass of the aporphinoid alkaloids are the oxoisoaporphines (7H-dibenzo[de,h]quinolin-7-ones, e.g., menisporphine, (2)), which at the first glance appear to be not derived

• synthetic, oxoisoaporphine-like analogues were found to have strong DNA binding affinity and therefore high cytotoxicity [5] as well as antiplasmodial activity [6]. Besides menisporphine (2), the related oxoisoaporphine alkaloids dauriporphine (3), 6-O-demethylmenisporphine (4), dauriporphinoline (5) and

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• Flexibacter spec.) (Figure 1) [1][2]. Elansolid A2 (1*), an atropisomer of elansolid A1 (1), showed antibiotic activity against Gram-positive bacteria in the range of 0.2 to 64 µg/mL and cytotoxicity against L929 mouse fibroblast cells with an IC50 value of 12 µg/mL. Besides these two macrocylic members also

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• , macrocyclic glycolipids have shown phosphatase inhibition, cytotoxicity and antiviral activities [12][14]. Generally, the synthesis of these molecules involves a multi-step construction of linear precursors incorporating synthetically compatible functional groups followed by a cyclization in the late stage of

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

• photoisomerization (not observed in the present study) can be attributable mainly to its higher vertical excitation energy (87.1 kcal/mol in 4a) relative to those of 2 (81.6 kcal/mol in 2a) and 3 (79.5 kcal/mol in 3a). Antifungal activity and cytotoxicity Compounds 1 and 4–6 and the mixture of 2 and 3 were evaluated

• of cycloheximide derivatives (4 vs 6) [21][22], and suggested that 2,3-dehydrogenation might result in the loss of the activity (1 vs 5, 6). The cytotoxicity of these isolates against human lung epithelial carcinoma (A549), human cervical epithelial adenocarcinoma (HeLa), and human breast carcinoma

• energies and selected geometrical parameters of key stationary points in S0, S1, and T1 potential energy surfaces of 2a/3a and 4a. Antifungal activity and cytotoxicity of 1–6a. Supporting Information Supporting Information File 176: HRESIMS, 1D and 2D NMR spectra of compounds 1–3; energies, populations

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

• Neuman-Keuls test) were performed with GraphPad Prism (v. 5.03) [52]. Cytotoxicity assays. The cytotoxicity of costic acid was investigated in human umbilical vein endothelial (HUVE) cells (PromoCell) by incubation with the cell proliferation reagent WST-1 (Roche, Mannheim, Germany) as previously

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• , demonstrating that in addition to N-dopant agents, Cl sources such as HCl, are key as SPAs that can improve the PL properties of FCDs. The Cl/N-doped CDs were incubated with WI38 and HeLa cell lines and the cell viability was studied by an MTT assay. It was found that no cytotoxicity was observed up to CD

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

• . Nakiterpiosin (117) is a marine sponge metabolite which demonstrates a potent cytotoxicity against the P388 leukemic cell line. The photo-variant of the Nazarov cyclization has been applied as one of the steps in the total synthesis of nakiterpiosin (117, Scheme 37) [63]. Starting from substrate 115, 1-indanone

• tirelessly exploring for better anticancer pharmaceuticals. Negi et al. have joined these efforts and proposed a synthesis of 2-benzylidene-1-indanones, which exhibited a strong cytotoxicity against four human cancer cell lines: breast (MCF-7), colon (HCT), leukemia (THP-1) and lung (A549) with IC50 values

• -indanones 132a–s were also investigated on the K562 human chronic myelogenous leukaemia cell line. The strongest cytotoxicity against the K562 cell line showed the following compounds: 132a, 132b, 132d, 132f, 132g, 132i, 132k, 132m, 132n, 132o with IC50 values in the range of 0.08–2.8 µM. The compound 132b

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

• compounds were evaluated for their activity against a large number of viruses. However, none of them showed significant antiviral activity or cytotoxicity. Keywords: analogue; antiviral; carbocyclic; nucleoside; phosphonate; Introduction Biomass is a valuable resource in search of renewable organic carbon

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• transfected with 15 pmol of the above mentioned DNA duplexes and Screenfect®, for 24 hours at a concentration, which was not toxic for the cells (see cytotoxicity test in Supporting Information File 1), and imaged by confocal fluorescent microscopy using the excitation wavelength of the energy donor (D1, λexc

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

• 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

• first exothermal peak of the plot of heat flow (mW/g) vs temperature. All measurements for each compound were run in triplicate and the results were averaged. Cytotoxicity test (MTT assay) The cytotoxicity assay (MTT) was evaluated for all test compounds as described in our earlier work [25]. Five