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

• derivatives have been shown to possess a variety of biological activities, such as antibiotic, antifungal and antiproliferative activity [47]. The combination of the antibiotic properties of piericidins and streptochlorin is most likely the reason for the effective inhibition of various entomopathogenic

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• endogenous metabolite of the most common estrogen hormone, 17β-estradiol, has been intensively studied owing to its proven potent antiangiogenic, antiproliferative and antitumoral activities [2][3]. However, its poor bioavailability has retarded its development as a drug [4][5]. Although recent reports of

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

• comparison with 21, compound 3 showed one extra aliphatic carbon and was named aplysinin B. The new compounds 14-debromo-11-deoxyfistularin-3 (1) and aplysinin A (2) were tested for their antimicrobial activity against different Gram-positive and Gram-negative bacteria, fungi, and for their antiproliferative

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

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

• structure of the natural product has been confirmed. When tested by the NCI against a range of human cancer cell lines, it was found that panicein A2 exhibits very little antiproliferative activity at 10 μM – an observation that is at odds with the earlier report that stated panicein A2 exhibits in vitro

• MEL28 human melanoma) with an ED50 of 5 μg/mL [3]. Panicein F1 (4) was active against P388, A549 and MEL20 cell lines (ED50 = 2.5 μg/mL). The diversity of antiproliferative activities shown by these compounds, and particularly panicein A2 (5), presents them to be attractive synthetic targets. We

• compared to control. These results indicated panicein A2 (5) to have poor antiproliferative activity and the possibility that the originally tested natural material was contaminated with trace amounts of an even more active compound. Conclusion In conclusion, the first total synthesis of aromatic

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

• and death. This explains why it is down-regulated during carcinogenesis and opens the door for nucleophilic addition of amines to 5,6α-EC as a new lead for developing potential anticancer drugs [15]. Apart from antimicrobial and antiproliferative activities of cholesterol derivatives, other

• different forms and with a hexyl spacer. Retaining the dimethylmaleoyl (DMM) group in targets 16 and 20 was based on the finding that NDMM-protected phosphatidylcholine showed better antiproliferative activity than its natural hydrochloride congener [38]. Thus, to prepare these targets glucosyl donor 14 [39

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

• h. Therefore, the second Negishi coupling needed to be performed with N,N-dimethylnicotinamidezinc chloride. Synthesis of pyridoacridine analogues The strong antiproliferative activities shown by these alkaloids inspired the design and the synthesis of many pyridoacridines analogues. Scheme 9 shows

• . Its structural motif, 7H-pyrido[2,3,4-kl]acridine fusing with a 2H-1,4-thiazin-3(4H)-one ring (Figure 11) seems to be less potent than that of 62 [46][79][80]. Ascididemin (42) demonstrated interesting antiproliferative activitiy and its pharmacophore 9H-quinolino[4,3,2-de][1,10]phenanthrolin-9-one

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• -(trifluoromethyl)phenyl)azole 1f or 2f (Figure 5) could be in relation with a reaction temperature (too high) not suitable to discriminate between similarly acidified positions. Antiproliferative activity in A2058 melanoma cells The N-arylated pyrroles and indoles exerted low to moderate antiproliferative activity

• antiproliferative activity, with no significant difference between the pyrrole and indole derivatives. Conclusion Unlike other azoles such as pyrazole and triazoles [37][38][40], pyrrole and indole do not possess any atom capable of coordinating metals. As a consequence, the corresponding CH acidities in THF

• substrates. Consequently, the Gibbs energy of the homodesmic reaction (ΔGr,sol) and the pKa value are related by the following equation: Biological evaluation. The antiproliferative activity of N-arylated pyrrole and indole derivatives was studied in the A2058 (ATCC® CRL-11147) cell line as described

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• , dimers 6 and 7 are nontoxic to PC12 cells at a concentration of 40 μM and, contrary to curcumin, dimer 7 protects PC12 cells against MnCl2 damage [11]. When the phenol OH groups of dimer 8 were protected with methyl or phenyl groups, antiproliferative activity against malignant melanoma cells was

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• 4.50–5.10 and 4.25–4.75 ppm, respectively in 13 and 14, as a doublet of doublets, for the methylene group at C-4’ position. Biological tests The antiproliferative effect of the obtained derivatives was tested on a panel of cell lines: african green monkey kidney cells (Vero and BS-C-1), human

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• hypoxia-inducible factor (HIF)-1-dependent luciferase expression [15], and possess potent antiproliferative effects on the human colon cancer cell line Caco-2 [16]. 3,7-Di-O-methylkaempferol (kumatakenin) demonstrates high inhibitory activity against porcine pancreas α-amylase [7]. 4′,7-Di-O

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• antiproliferative effects [55] that strongly inhibit angiogenesis in both in vitro and in vivo models. Mechanistically, it interferes with MMP-2 and a urokinase plasminogen activator (uPA) [56]. However, due to its instability in aqueous solution, complex structure and limited availability, hyperforin is neither a

• drug candidate nor a good model compound. The finding that structurally simpler, natural, acylphloroglucinol derivatives also showed antiproliferative effects against endothelial cells with inhibitory effects in a tube-formation assay on Matrigel catalyzed the search for simple acylphloroglucinols with

• anti-angiogenic activity. Within this group, some geranylated monocyclic and bicyclic acylphloroglucinol derivatives have been identified that are structurally much more simple than hyperforin. However, they exhibiting potent antiproliferative activity for a human microvascular endothelial cell line

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

• within the polynucleotide binding site. All 4,9-DAP derivatives also showed considerable antiproliferative activity, interestingly only 19 having strong, micromolar activity in vitro but negligible in vivo toxic effects in mice [97]. Strong fluorescence of 19 allowed monitoring of the very efficient

• analogue, dihydroimidazophenanthridinium cation characterised by cyclic structure connecting positions 5 and 6, showed promising antiproliferative activity [3][98][99]. Molecular modelling results and some preliminary experiments suggest intercalative binding mode, however up till now interactions with

Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light “on water”

• Julio Benites,
• Juan Meléndez,
• Cynthia Estela,
• David Ríos,
• Luis Espinoza,
• Iván Brito and
• Jaime A. Valderrama

Beilstein J. Org. Chem. 2014, 10, 2448–2452, doi:10.3762/bjoc.10.255

• -7) cancer cells. These results and our continuous interest in the synthesis of aminoquinones for antiproliferative evaluation [11][12][13], prompt us to explore a straightforward access to potential antiproliferative aminojuglone-analogues of compound 3. The study led us to discover a potential and

Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

• Xiang Zhou,
• Jacqueline E. Reilly,
• Kathleen A. Loerch,
• Raymond J. Hohl and
• David F. Wiemer

Beilstein J. Org. Chem. 2014, 10, 1645–1650, doi:10.3762/bjoc.10.171

• should reduce cellular levels of GGPP and thus diminish protein geranylgeranylation, one might expect that inhibitors of this enzyme would interfere with essential cell signaling pathways and demonstrate antiproliferative activity. Several years ago we reported the synthesis of digeranyl bisphosphonate

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• -positive and Gram-negative bacteria, fungi, and for antiproliferative activity. The results given in Table 4 show that siphonodictyal E3 (3) and cyclosiphonodictyol A (5) exhibited mild activity against the Gram-positive bacteria Staphylococcus aureus and Micrococcus luteus, while siphonodictyal E4 (4

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3. Keywords: ansamitocins; antibiotics

• , we demonstrated that the ansamitocins (maytansinoids) 3–5 are an ideal showcase for creating small libraries by mutasynthesis [8][9][10]. These secondary metabolites exert strong antiproliferative activity towards different leukemia cell lines as well as human solid tumors. Inhibitory concentrations

• still strong antiproliferative activity (IC50 < 10 nM) for different cancer cell lines. Importantly, the intact conjugate showed strong antiproliferative activity for a FR+ cancer cell line but was inactive against a FR− cell line. Indeed, despite the substantial size of the substituent remaining at C19

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• . The isolated compounds were tested for their bioactivity in a series of antimicrobial and antiproliferative assays. We found that apart from compounds 1 and 2, the other isolates (3–8) inhibited the conidial germination in Magnaporthe oryzae at concentrations of 50 µg/mL or less (Table 3) whereas the

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• aglaforbesin A (1) and pyramidatin (4) for pyramidaglain (3) as shown in Figure 1 [3]. The benzopyran and benzoxepine containing flavaglins showed insecticidal, antifungal and antiproliferative activity against various cancer cell lines [4]. Apart from acting as precursors for flavaglins, some of the cyclic

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• pyrazolo[4,3-d]pyrimidine sildenafil. In addition, trapidil is a [1,2,4]triazolo[1,5-a]pyrimidine compound, which is the first triazolopyrimidine registered as a drug possessing antiproliferative activity in glioma cells and vascular smooth muscle cells (VSMCs) and used as a coronary vasodilator in the

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