The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• mimicking several aspects of the adenosine moiety, by induced-fit structural changes and the conformational flexibility of the enzyme residues (Figure 3). Together with several related analogues, 26 displays significant cytotoxic and antiproliferative effects [19]. Due to the key role of protein kinases in

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• show four valine residues. The structures of the compounds, isolated along with the known theonellapeptolide Id, were determined by extensive 2D NMR and MS/MS analyses followed by application of Marfey’s method. The isolated peptides exhibited moderate antiproliferative activity against HepG2 cells, a

• hepatic carcinoma cell line. Keywords: antiproliferative activity; cyclic peptides; marine metabolites; theonellapeptolides; 2D NMR; Introduction Three decades of extensive chemical investigation [1] have clearly evidenced that marine sponges of the genus Theonella (Lithistida, Theonellidae) are

• during the present investigation (1–3) have been evaluated for their antiproliferative activity against HepG2 cells, a hepatic carcinoma cell line. As reported in Figure 4, all tested compounds showed antiproliferative activity at low micromolar doses, with a similar pattern of potency. At the dose 10 μM

A study on electrospray mass spectrometry of fullerenol C₆₀(OH)₂₄

• Mihaela Silion,
• Andrei Dascalu,
• Mariana Pinteala,
• Bogdan C. Simionescu and
• Cezar Ungurenasu

Beilstein J. Org. Chem. 2013, 9, 1285–1295, doi:10.3762/bjoc.9.145

• m/z 279 and [M − 12H2O + 2NH3 + 6H]6+ at m/z 158. Keywords: electrospray; fullerenol C60(OH)24; mass spectrometry; Introduction Because of their potential for chemical tunability and exciting range of biological activities as glutamate-receptor antagonists [1] and antiproliferative [2][3

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• intermediate for the synthesis of (−)-agelastatin A (AA, 1), a potent antiproliferative alkaloid. The present synthetic endeavour offered an insight into the mechanism underlying the iron(II)-mediated aminohalogenation of N-tosyloxycarbamate, in which the radical properties of the N–iron intermediates in the

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• -naphthoquinone structure is common for various natural products. It is associated with numerous biological activities, such as enzyme-inhibitory, antifungal, antibacterial, anticancer, antiproliferative, antiplatelet, anti-inflammatory, antiallergic, and antimalarial ones. Benzoquinones fused with heterocycles

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• incubation time (Table 1). Phalloidin displayed no antiproliferative activity up to a concentration of 10−3 M in the culture medium. In contrast, the most lipophilic ester derivative, phalloidin oleate (1e), showed an IC50 value of proliferation inhibition of 2.5 × 10−6 M, and was thus ca. 1000 times more

• , were highly toxic for mouse fibroblasts, and their antiproliferative activity was comparable to the most lipophilic derivative, phalloidin oleate (Figure 4a). Their toxicity was found to be dependent on the configuration of the polymer, since phalloidin bound to D-configurated polylysine was about 10

Reactions of nitroxides XIII: Synthesis of the Morita–Baylis–Hillman adducts bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as a starting compound, and DABCO and quinuclidine as catalysts

• Jerzy Zakrzewski

Beilstein J. Org. Chem. 2012, 8, 1515–1522, doi:10.3762/bjoc.8.171

• ones [21][22][23][24]. Some recent results concerning MBH reaction have been presented [6][16][18][25][26][27][28][29][30][31][32][33]. MBH adducts themselves are reported to be antiproliferative agents [34]; however, they are often applied as a tool for building more complex target structures, usually

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• mutants and mutasynthetic approaches. We suggest that the formation of these derivatives is based on elimination at C-7/C-8 followed by reduction(s) of the intermediate enone. In bioactivity tests, only ansamitocin derivatives bearing an ester side chain at C-3 showed strong antiproliferative activity

• -proansamitocin 8 (3.5 mg/L) and two diastereomeric byproducts 9a and 9b (7.6 mg/L; 1:1 ratio) from the fermentation broth of A. pretiosum Δasm12/21 (Figure 1). We also showed that none of these proansamitocin derivatives exhibit antiproliferative activity. Herein, we describe the unprecedented formation of

• )ansamitocin derivatives lacking the ester side chain at C-3 (11b, 11g–h, 12–16) do not show any antiproliferative activity (IC50 > 800 nM) for at least two of the cell lines listed in Table 1. Compounds 11c–e, bearing the ester side chain at C-3, predominantly showed activities in the pM range. As seen also

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• activity towards three cancer cell lines (NCI-H460, MCF7 and SF268). Marilone A and C (1, 3) showed weak antiproliferative activity with an average GI50 of 36.7 and 26.6 µM, respectively (see Supporting Information File 1). Marilone B (2) was assayed in a panel of 44 psychoactive receptors, including 11

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• majuscula strain found in Curacao, and it exhibits potent antiproliferative and cytotoxic activities [44]. This intriguing structure contains a thiazoline and a cyclopropyl ring. Interestingly, the pathway comprises a HMG-CoA synthase cassette, highly similar to the one of the jamaicamide assembly line

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• , PA 15260, USA Department of Pharmaceutical Sciences, School of Pharmacy, 3501 Terrace Street, University of Pittsburgh, Pittsburgh, PA 15261 USA 10.3762/bjoc.7.161 Abstract The dictyostatins are powerful microtubule-stabilizing agents that have shown antiproliferative activity against a variety of

• microtubule-stabilizing agents include taxanes, epothilones, and discodermolides, among others [3][4]. Dictyostatin (1a) is an exceptionally potent microtubule-stabilizing agent that has shown antiproliferative activity in a variety of human cancer cell lines in the low nanomolar range. Isolated first in 1994

Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

• Sławomir Boncel,
• Maciej Mączka,
• Krzysztof K. K. Koziol,
• Radosław Motyka and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2010, 6, No. 34, doi:10.3762/bjoc.6.34

• against it within the group tested. Very recently, Accetta et al. reported remarkable symmetrical amide-conjugated bis-α,ω-uracil based systems (IV). These compounds exhibited antiproliferative and erythroid differentiation induction properties towards human chronic myelogenous leukaemia K562 cells [3

Microwave assisted synthesis of triazoloquinazolinones and benzimidazoquinazolinones

• Aboul-Fetouh E. Mourad,
• Ashraf A. Aly,
• Hassan H. Farag and
• Eman A. Beshr

Beilstein J. Org. Chem. 2007, 3, No. 11, doi:10.1186/1860-5397-3-11

• ] anticancer, [5] anti-inflammatory, [6] anticonvulsant, [7] and antiproliferative activities as well as inhibitory effects for thymidylate synthase and poly-(ADP-ribose) polymerase (PARP). [8] An interesting method for quinazoline synthesis involved [5+1] annulation during the reaction of β-dicarbonyl

Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel

• Karunananda Bombuwala,
• Thomas Kinstle,
• Vladimir Popik,
• Sonal O. Uppal,
• James B. Olesen,
• Jose Viña and
• Carol A. Heckman

Beilstein J. Org. Chem. 2006, 2, No. 13, doi:10.1186/1860-5397-2-13

• combination had antagonistic effects. Other researchers found that the antiproliferative effect of paclitaxel was relatively little affected by the presence of microtubule depolymerizing agent, N-acetylcolchinol [50]. Workers who studied cells cultured in vitro found high IC50 levels, in the 10–50 nM range

• , for antiproliferative activity of paclitaxel and vinorelbine individually, but synergy with concentrations as low as 3 nM and 0.01 nM respectively [51]. Thus, differing model systems yielded results variously suggesting antagonistic, non-additive, or synergistic effects. However, there is evidence