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

• with Scheffe's test. The level of statistical significance was set at p < 0.05. Preparation scheme of Lac-β-CyD. MALDI–TOF MS (A) and 1H NMR (B) spectra of Lac-β-CyD. Cytotoxic activity of β-CyDs in U18666A-treated HepG2 cells after treatment for 24 h. U18666A-treated HepG2 cells were incubated with

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

• cytotoxic activity. Classical agar diffusion assays were performed using the fungus Aspergillus niger, the yeast Saccharomyces cerevisiae as well as the Gram-negative bacterium Escherichia coli, and the Gram-positive bacterium Micrococcus luteus and Mycobacterium phlei as test organisms. In agar diffusion

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• hydroquinoline derivative 327 in 81% yield. Further, they have used the bicyclic compound 327 as a key building block in the total synthesis of (+)-luciduline (Scheme 71). Lepadins are natural products consisting of cis-fused decahydroquinoline subunits and they display cytotoxic activity against many human

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

• synthetic compounds, has been widely investigated. Many of them displayed cytotoxic activity in addition to other bioactivities such as antiviral, antifungal, antibacterial, antitumor and antiparasitic potential [41]. Several reviews on pyridoacridine alkaloids have been published between 1983–2015 [35][43

• pyridoacridines interestingly displayed strong (IC50 < 10 µM) cytotoxic activity in vitro. For instance, pantherinine (69) isolated from Aplidium pantherinum [77] and cystodytins A–G (70–76) from Cystodytes dellechiajei [36][78] are all potent anticancer metabolites. Their structures are based on a 4H-pyrido

• cell lines [57][69]. As shown in Figure 13, the cytotoxic activity slightly improves when the OH group of the E ring of 56 is oxidized to afford 82 [82]. This bioactivity significantly increases with more selectivity without any substituent on the 8H-benzo[b]pyrido[4,3,2-de][1,7]phenanthrolin-8-one

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• recognized as active agents against tuberculosis and malaria [3][7], cardiovascular diseases [3], and cancer [4]. Cinnamates show depigmenting [4], antidiabetic, antihyperglycemic, anticholesterolemic, anti-inflammatory, hepatoprotective, CNS depressant, anxiolytic, and cytotoxic activity [7]. Cinnamate

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 development of major mycobacterial resistance [19]. Patchy cytotoxic activity was seen with the N-substituted isatins 32, 33, and 34. Compounds of this general type, but incorporating N-arylmethyl as well as 5,7-dibromo substituents, have given rise to potent anticancer compounds with activity

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• with IC50 values of 34.77–45.68 μM. Keywords: cytotoxic activity; neolignans; Trogopterus xanthipes; Introduction Chemical studies of natural products including ones derived from plants and microorganisms have led to the isolation of numerous novel metabolites with biological activities [1][2]. As a

• controlling of antithrombin levels, inhibition of platelet aggregation, cytotoxic activity, immunity enhancement, and anti-inflammatory activities. Isolation of compounds from the methanol extract of Trogopterus feces was presented before by our group [12]. In the present investigation, chemical evaluation of

• of 34.77–45.68 μM using adriamycin as a positive control (IC50 = 0.18 μM). Additionally, compound 1 showed very weak cytotoxic activity against MCF-7 cells with an IC50 of 94.69 μM. None of the compounds affected the HeLa cells. Conclusion In summary, two novel neoligans (trogopterins A and B) and a

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

• combined with moieties covalently interacting with DNA and RNA. One of the most promising examples reported recently revealed that in a series of mono functional, cationic platinum(II) compounds, phenanthriplatin displayed a greater cytotoxic activity than either cisplatin or oxaliplatin despite a fact

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• desposit@ccdc.cam.ac.uk. Biological assays Cytotoxic activity against 11 human cancer cell lines, K562 myeloid leukemia, SH-SY5Y beuroblastoma, SGC-7901 gastric adenocarcinoma, HepG2, SMMC-7721 hepatocellular carcinoma, A549 lung cancer, MCF-7, MDA-MB-231 breast cancer, HCT116, SW480 colon cancer, HT29

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• these compounds is of particular interest as 2-prenyltryptophan derivatives have been obtained or isolated from a diverse array of natural sources [66][67] and, in general, prenylation at the indole ring leads to a significant increase in the antioxidant and/or cytotoxic activity of tryptophan

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• a tetrasubstituted trans-cyclopropane subunit. The compound shows modest cytotoxic activity against murine melanoma cells [98][99]. The first enantioselective total synthesis of anthoplalone was achieved by Hanessian and co-workers and utilized their chloroallyl phosphonamide anion cyclopropanation

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• our cationic carbonyl-substituted titanocenes. Comparison of the three most active complexes also allows the identification of structural features essential for cytotoxic activity. First, a bulky substitution of the cyclopentadienyl ligand is favorable. Second, positioning of the triazol in close

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• ][8] and display both antibiotic and cytotoxic activity [9]. They have a polycyclic xanthone aglycone in common, which is glycosylated at the C14–OH group. In Figure 1 the structure of kigamicin B, which carries a D-amicetose disaccharide unit, is shown as a representative example. Another antitumor

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

• ) show cytotoxic activity against the L929 mouse fibroblasts, KB-31 epidermoid carcinoma, and the breast cancer cell line MCF7, although none of them showed activity in the antimicrobial assays against Gram-negative bacteria and the fungus Candida albicans. Many of the isolated compounds from Aka

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

• Enterococcus (VRE) [159]. Beyond that, the modest cytotoxic activity of 215 and 217 against human cancer cell lines makes them interesting lead components for drug discovery. The IC50 values of 215 for different leukemia cell lines range from 0.11–0.22 µM. For 217, an IC50 value of 0.32 µM against gastric

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• from (−)-isopulegol [5]. Remarkably, its cinnamate [(−)-9-deoxyenglerin A] displayed a cytotoxic activity in the μM range against several cancer cell lines [5]. Herein we report a concise enantioselective access to (−)-oxyphyllol (1) in a few preparatively simple operations. Results and Discussion

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• naphthalene analogue, yet without totally explaining the observed cytotoxic activity of the compounds. Finally, a synthetic entry is given to the complete carboheterocyclic core of aurachin H through the N-oxidation/epoxidation of aurachin D and a shorter chain analogue, followed by subsequent biomimetic

• (6) and related compounds in a bio-inspired manner. Biological activities The cytotoxic activity of aurachin D (4) and analogues 9–11 and 17–19 was evaluated in growth inhibition experiments on mammalian cell lines (Table 2). After 5 days treatment, half inhibitory concentrations (IC50) were

• inactive in the tested concentration range, although aurachin analogue 18 was determined to have a cytotoxic activity (IC50) at ca. 1 µg/mL. This might be due to differential effects on different cell lines, a different time course of electron-transport inhibition, or a different mode of inducing apoptosis

Lanostane- and cycloartane-type triterpenoids from Abies balsamea oleoresin

• Serge Lavoie,
• Charles Gauthier,
• Jean Legault,
• Sylvain Mercier,
• Vakhtang Mshvildadze and
• André Pichette

Beilstein J. Org. Chem. 2013, 9, 1333–1339, doi:10.3762/bjoc.9.150

• against human cell lines (A549, DLD-1, WS1) and their antibacterial activity against E. coli and S. aureus. Abiesonic acid (6) exhibited weak cytotoxic activity against A549 (IC50 = 22 µM) while compounds 1 and 4 were weakly active against S. aureus (MIC = 25 µM). Keywords: Abies balsamea; cycloartane

• (WS1) using the resazurin reduction test [25]. Etoposide was used as a positive control (IC50 ≤ 1.0 µM). None of the compounds were found to be active (IC50 > 25 µM) with the exception of abiesonic acid (6), which showed a weak cytotoxic activity against A549 (IC50 = 22 µM). The antibacterial activity

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• psammaplin A thiol (4), and SAHA (1) were included as control compounds. The results are shown in Table 1. IC506/1 is defined by the ratio IC50HDAC6/IC50HDAC1 and was used as an indicator of isoform selectivity in vitro. The synthesised thioesters displayed modest but significant cytotoxic activity in our

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

• al. [31]. Compounds 1a–1e represent a series of phalloidin derivatives with increasing log Pow values. At the same time they represent a series of phalloidin derivatives with increasing cytotoxic activity. Since the two parameters are linearly related (Figure 3), we conclude that the amount of toxin

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• important tubulin-binding cytotoxic drug, was shown to retain the cytotoxic activity of the parent compound. At the same time nonspecific side effects due to oxidative degradation were prevented by the introduction of the CF3 group [14][15]. Likewise, partially fluorinated taxoids, analogues of paclitaxel

Bioactive selaginellins from Selaginella tamariscina (Beauv.) Spring

• Chao Yang,
• Yutian Shao,
• Kang Li and
• Wujiong Xia

Beilstein J. Org. Chem. 2012, 8, 1884–1889, doi:10.3762/bjoc.8.217

• -formyl-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene]cyclohexa-2,5-dien-1-one. Compound 1, 2 and 3 exhibited appreciable cytotoxic activity against cultured HeLa cells (human cervical carcinoma cells), as well as significant antioxidant activity. Keywords: antioxidant

• were assigned in Table 2. Several species of the genus Selaginella have long been used in traditional medicine as anticancer agents, but only limited literature information on the cytotoxic activity of their constituents is available, which encourages us to investigate the cytotoxic effect of the

• seleginellins [4][5][7]. The cytotoxic activities of the three selaginellins: selaginellin O (1), selaginellin M (2) and selaginellin (3) were evaluated by using human cervical carcinoma (HeLa) cells. It is noticeable that all of these selaginellins exhibited appreciable cytotoxic activity (Supporting

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• with enhanced antimicrobial potency and weak cytotoxic activity. The first step in this process was to select an appropriate sequence to serve as the peptide scaffold. Many linear AMPs are unstructured in aqueous solution and only adopt a well-defined structure in the presence of a lipid bilayer [1

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• hemocytes of 30 (compound 3), 1.7 (compound 6), and 103 (compound 9) (Table S7). Compounds 3, 5, 6, and 9 are active in the MCF-7 assay with EC50 [µg ml−1] values of 58, 363, 26, and 34, respectively. Similar to previous results [19], several tryptamine amide derivatives (20–24, 26) showed cytotoxic

• activity against the MCF-7 cells with 24 being the most potent compound (1.02 µg ml−1). Interestingly, 26 also showed activity against Galleria hemocytes, although its oxazole derivative 10 did not, which may point to different targets for both compound classes. The class of oxazole compounds, which were

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

• as described by Shimokawa et al. [21]. Cytotoxic activity assay against a panel of three cancer cell lines, NCI-H460, MCF7 and SF268 at the 100 µM level was performed according to Saroglou et al. [22] and Monks et al. [23]. Compounds were tested for antiplasmodial activity against Plasmodium berghei

• berghei (see Supporting Information File 1). Interestingly, marilone C (3) showed no activity at 25 µM concentration, indicating that the methyl group 11-CH3 and/or the position of the ketone functionality is essential for this bioactivity. Marilones A, B, and C (1–3) were also tested for cytotoxic

• 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