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

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• previously mentioned compounds were synthesized in order to evaluate their antiviral and cytotoxic activity. Moreover, antibacterial activity of some of these derivatives has also been studied. Some of the tested compounds have shown interesting results and a brief survey is given in the following section

• -kinase (TK) positive and negative strains of Herpes simplex virus type-1. All of these 2'-deoxyuridine analogues exhibited only weak anti-HSV-1 activity. Cytotoxic activity Only a few derivatives have been tested for their anticancer properties. The cytotoxic activity for derivatives 12, 13 and 28

• (Figure 12) were determined by an in vitro L1210 assay [9][10]. However, a comparison of the results for the investigated compounds with those of the reference compound melphalan showed lower activity. Recent studies on cytotoxic activity of 5-[alkoxy-(4-nitrophenyl)methyl]uracil analogues 124, 126 and

C–C (alkynylation) vs C–O (ether) bond formation under Pd/C–Cu catalysis: synthesis and pharmacological evaluation of 4-alkynylthieno[2,3-d]pyrimidines

• Dhilli Rao Gorja,
• K. Shiva Kumar,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2011, 7, 338–345, doi:10.3762/bjoc.7.44

• -alkynylthieno[2,3- d]pyrimidines were prepared via alkynylation of 4-chlorothieno[2,3-d]pyrimidines in good to excellent yields. Some of the compounds synthesized were tested for cytotoxic activity in vitro. Keywords: catalysis; C–C bond; copper; palladium; thieno[2,3-d]pyrimidine; Introduction Alkynyl

• further structural elaboration leading to the functionalized derivatives of thieno[2,3-d]pyrimidine preparation which may be difficult to access by other methods. Some of the 4-alkynyl-derivatives synthesized were screened for their cytotoxic activity against chronic myelogenous leukemia (CML) cell line

• methanol.a Cytotoxic activity of 4-alkynylthieno[2,3-d]pyrimidines (3) against chronic myelogenous leukemia (CML) cell line. Supporting Information Supporting Information features details on experimental procedures and spectral data as well as NMR spectra of compounds 3a–n. Supporting Information File 89

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• can be identified in the clinical antitumor agents etoposide, teniposide [21] and lignan lactone podophyllotoxin [22], and structure–activity relationships have shown that the methylenedioxy moiety is fundamental for cytotoxic activity since it can be metabolized by CYP to form metallo–carbene

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• [41]. Total synthesis of mosin B Mosin B (94) is a mono-THF acetogenin isolated by McLaughlin’s group [47] from the bark of Annona squamosa and shows selective cytotoxic activity against the human pancreatic tumor cell line, pancreatic cancer cells (PACA-2) (ED50 = 2.5 × 10−4 µg/mL), with a potency

• the seed of Annona muricata by Cortes’s group [51], which shows selective cytotoxic activity against human lung carcinoma (A-549) (ED50 = 5.90 × 10−8 µg/mL), human colon adenocarcinoma (HT-29) (ED50 = 6.58 × 10−8 µg/mL), and human kidney carcinoma (A-498) (ED50 = 1.09 × 10−9 µg/mL) with potency from

• ). Squamocin A (181a) [76] (also called annonin I [74]) and squamocin D (188) [77] (also called asiminacin [78]) belong to a subclass of ACGs with an adjacent bis-THF subunit and an extra hydroxy group in the left side chain (C-28). Both natural products show remarkable cytotoxic activity and are interesting