Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• inhibited 10 out of the 24 kinases tested. The results of the MTT and the kinase assay showed a similar pattern, and hence it was concluded that protein kinase inhibition should be one mechanism leading to the cytotoxicity of 17. In a study using human colon carcinoma cells to elucidate the cell death mode

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• Hergenrother and it was found to have low cytotoxicity, enter DM1 model cells, dissolved the MBNL1 foci and partially corrected the missplicing of two key pre-mRNAs, cTNT and IR. A terrific collaboration with Professor Edwin Chan’s group at the Chinese University of Hong Kong allowed the compounds to be tested

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards

• to increase water solubility, stability and bioavailability of those drugs [56][57]. In such a way, the bioavailability of genistein was found to be increased by complexation with CDs [58]. Cytotoxicity to cancer cell lines The cytotoxicity of flavanones and their inclusion complexes against three

• -loaded nanoparticles which exhibited significant cytotoxicity at high concentrations (30, 40 and 50 μg/mL) [59]. At low concentration (0.025 mM), naringenin complexed with DM-β-CD exerted a higher effect on MCF-7 and HeLa cells than free naringenin. However, for CaCo-2 cells, the effect of the naringenin

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• CuSO4·5H2O and sodium ascorbate in DMF [35][36]. All the obtained compounds were evaluated for in vitro cytotoxicity against a panel of five human cancer cell lines, where compounds 45 and 46 displayed the highest and broadest spectrum activity against all five cancer cell lines under study (Scheme 16

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

• of 1 and 2 were confirmed by an 1,1-ADEQUATE experiment. Compounds 1 and 2 showed a mild to moderate cytotoxic activities against KB-31 and FS4-LTM cell lines. Only aplysinin A (2) exhibited cytotoxicity against MCF-7 cells. Keywords: alkaloids; Aplysina lacunosa; bromotyrosine; marine natural

• luteus; Gram-negative: Peumonia aruginosa and Klebsiella pneumonia] and antifungal Candida albicans using microdilution technique. The MIC was defined as lowest concentration that shows 50% growth inhibition after 24 hour incubation. Cytotoxicity assay The cytotoxicity was determined using WST-1 cell

• ), hexadellin B (10), and diacetylhexadellin B (20). NMR data of aplysinin B (3) (600 MHz, DMSO-d6) and compound 21. Cytotoxicity of the isolated compounds (IC50).a Supporting Information Supporting Information File 448: 1D, 2D NMR, and CD spectra of three new compounds. 1D NMR, mass and CD spetra of all known

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

• preliminary result suggests that the inclusion ability of Lac-β-CyD is still maintained. Cytotoxicity of Lac-β-CyD To reveal the cytotoxicity of Lac-β-CyD, we examined the WST-1 method (Figure 3). Here, we used U18666A-treated HepG2 cells as NPC-like cells, because U18666A inhibits an intracellular

• cholesterol trafficking and has the potential to induce NPC disease phenotype [16]. No significant cytotoxicity of Lac-β-CyD was observed in U18666A-treated HepG2 cells at 1 mM for 24 h. The following studies were performed under the experimental conditions. Cellular uptake of TRITC-Lac-β-CyD To reveal

• cells, which accumulate the cholesterol and sphingolipids in cells, were prepared by the treatment with DMEM containing 1.25 μM U18666A for 48 h. Cytotoxicity In a similar manner as described in [30], cytotoxicity was assayed by the WST-1 method. Briefly, U18666A-treated HepG2 cells were seeded at 3

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

• mice fibroblasts. Only minor antimicrobial activities were obtained for citrinamines B–D (2–4) whereas no activities were found in the cytotoxicity assay for citrinamines A–D (1–4). Experimental General experimental procedures 1H, 13C, and 15N NMR spectra were conducted on Bruker Avance I 400 MHz

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

• cytotoxicity against a number of tumour cell lines. Keywords: modified Claisen rearrangement; sesquiterpene; chromenol; total synthesis; Introduction The panicein family is an unusual family of natural products, which generally consist of an aromatic sesquiterpene group linked to a quinone (as seen in

• isolated in 1994 from Reniera mucosa alongside its non-cyclised isomer 1, and ten other members of the panicein family [3]. Panicein A2 (5) and D (2) were reported to exhibit in vitro cytotoxicity against four cancer cell lines (P388 mice lymphoma, A549 human lung carcinoma, HT29 human colon carcinoma and

• with the earlier report that stated 5 exhibits in vitro cytotoxicity against a number of cell lines (ED50 = 5 μg/mL). Members of the panicein family of aromatic sesquiterpenoids. Proposed biogenesis of panicein A2 (5). Retrosynthetic analysis of panicein A2 (5). Synthesis of ketone 13. Synthesis of

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

• IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro. Keywords: antimicrobial; chalcone; cholesterol; cytotoxicity; glycoside; triazole; Introduction Cholest-5-en-3β-ol (cholesterol, 1

• antifungal activities against the filamentous fungal strain Aspergillus flavus (Link) and the yeast forming fungal strain Candida albicans (ATCC 7102) were moderate compared with amphotericin B in vitro. In the cytotoxicity study, this derivative was the most cytotoxic one against the prostate cancer PC3

• cytotoxicity of a lactose scaffold with a cholesterol moiety at the C-3 carbon of the B ring of the lactose. This is because chemically modified 3β-lactosides were emerged as potential galectin-3 inhibitors. Galectin-3 is a member of the protein family known as galectins and this subfamily is believed to be

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• Dactylospongia [24] and has significantly lower cytotoxicity. The absolute configuration of the natural material is not firmly established due to discrepancies in optical rotation values between natural and synthetic samples [25]. Zampanolide and dactylolide have engendered world-wide interest from the synthetic

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

• ] that summarize their bioactivity. Herein, a synopsis of the newly published bioactivity of pyridoacridine will be provided as well as pharmacophores associated with the activity and a discussion on the evolution of the bioactivity and the structure modification. Cytotoxicity The biologically tested

• [2,3,4-kl]acridin-4-one scaffold which could be considered as the pharmacophore. The cytotoxicity of 69–76 changes depending on the substituents attached to the benzoquinone moiety (Figure 10). Furthermore, shermilamines C (28), D (77) and F (30) also represent one of the interesting anticancer alkaloids

• at C-3 (80 and 81, Figure 12) [81]. Meridine (56) has shown moderate cytotoxicity against an array of cancer lines; nevertheless, it remains a candidate for the design of new and useful anticancer candidates. Some of its reported analogues have shown interesting cytotoxicity against various cancer

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• fungal β-N-acetylhexosaminidase evaluated [28]. Similarly, dimers of sylibin (11a,b, Figure 3) and dehydrosylibin, obtained by Novozyme 435-catalyzed acylation with the divinyl esters of dodecanedioc acid, were evaluated in terms of antioxidant activity and cytotoxicity [29]. The obvious hypothesis

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• them to serve as biomaterials. Conclusion In conclusion, we designed eight conjugates by modifying two endogenous binding peptide motifs with nucleobase and glucosamine (or not) and investigated their gelation properties, biostability, and cytotoxicity. Particularly, the mixture of 5 and 8 affords a

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• monocation, dication, and dianion of substantial stability. Riccardin C (96) is a macrocyclic bis-bibenzyl entity with pharmacological properties, including antimycotic and antibacterial effects, and cytotoxicity against P-388 mouse leukaemia and KB cell lines from nasopharyngeal carcinoma. In view of these

• licheniforme. These paracyclophane derivatives exhibit potent cytotoxicity against the KB and LoVo tumor cell lines (IC50 = 2–10 μg/mL). On another occasion, Smith and co-workers have reported the synthesis of (−)-cylindrocyclophane A (156) and (−)-cylindrocyclophane F (155) [144]. The dialkenyl derivative 152

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• , arginine (Arg) and histidine (His). To investigate the effects from introducing Arg and His to dPG, the resulting polyplexes of amino acid functionalized dPG-NH2s (AAdPGs)/siRNA were evaluated regarding cytotoxicity, transfection efficiency, and cellular uptake. Among AAdPGs, an optimal vector with (1:3

• ) Arg to His ratio, showed efficient siRNA transfection with minimal cytotoxicity (cell viability ≥ 90%) in NIH 3T3 cells line. We also demonstrated that the cytotoxicity of dPG-NH2 decreased as a result of amino acid functionalization. While the incorporation of both cationic (Arg) and pH-responsive

• residues (His) are important for safe and efficient siRNA transfection, this study indicates that AAdPGs containing higher degrees of His display lower cytotoxicity and more efficient endosomal escape. Keywords: arginine; dendritic polyglycerolamine; histidine; multivalent vector; siRNA delivery

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 carbonyl group, for future SAR studies. In addition, with compounds of the non-spirocyclic type 8 and 9 good antiplasmodial activity was also seen, with 8 being the most potent (IC50 1.94 µg/mL, 5.20 µM) of the compounds tested here. In order to further assess selective cytotoxicity, the toxicity

• of 9 towards Vero cells [18] was attempted but its autofluorescence precluded a result being obtained. These spiro heterocycles, indoloazepinoindol-17-one and azepinodiindolo compounds constitute new antiplasmodial structural leads with potentially new modes of action. Modest cytotoxicity against all

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• oxidation products cause many diseases, coronary heart disease and atherosclerosis being among the most common in modern societies [8][9][10][11]. Cholesterol oxidation products have also been proven to exhibit cytotoxicity as well as apoptotic and pro-inflammatory effects [12][13]. Therefore, in-depth

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

• can interact with intracellular targets to induce cytotoxicity [28][29][30][31][32]. Several functionalities have been inserted as linkers on the 2’-oxa-3’-aza-4’a-carbanucleoside skeleton in order to confer novel mechanisms of action for nucleoside mimics: in this context, the 1,2,3-triazole unit

• different biological effect with respect to 2’-oxa-3’-aza-4’a-carbanucleosides devoid of the triazole unit, such as compounds 2 and 8, which are endowed with antiviral activity, but do not show any cytotoxicity The ability of compounds 13a–g and 14a–g to interfere with the replication of different DNA and

• maintenance medium (DMEM with 2% heat inactivated FCS) was used to culture the viruses. Cell viability. The cytotoxicity of the tested compounds was evaluated by measuring the effect created on cell morphology and/or cell growth (cytostatic activity). Cell monolayers were prepared in 24-well tissue culture

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

• -methylkaempferol exhibits modest cytotoxicity [17]. These methylated derivatives of flavonols are found as natural products in relative low quantity, whereas kaempferol is relatively rich in plants. Therefore, it is quite worthwhile to develop procedures for the preparation of methylated derivatives of kaempferol

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• of the therapy. Another major factor is that anticancer drugs have a wide distribution capacity in the body and owing to non-selective cytotoxicity of these drugs not only the cancer cells but also healthy cells are killed. Due to low therapeutic indices of anticancer drugs, a rapid increase and

• cell line by the USP to test toxicity of polymeric systems and thus used in this study to investigate whether the toxicity of nanocapsules is associated with the polymer material itself or not. Therefore cytotoxicity of blank anionic and cationic CD nanocapsules was evaluated against L929 cells with an

• nanocapsules, physicochemical characterization of CPT-loaded CD nanocapsules, determination of CPT loading, in vitro CPT release studies, CPT stability in simulated GI fluids and cytotoxicity, anticancer efficacy and permeability assay of CD nanocapsules. Supporting Information File 140: Experimental data

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• structures as well as simple Ugi products exhibit promising biological profiles, e.g., cytotoxicity [13][19][20], fungicidal [21][22] and antibacterial properties [23][24][25][26], or inhibition of histone deacetylases [27]. The Ugi post-modification strategy has also been employed in the synthesis of

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• rings) are unexpected, novel, secondary metabolites, isolated from the marine-derived fungus Aspergillus ostianus strain 01F313 in bromine-modified 1/2PD culture medium [1][2][3][4]. Interestingly, these compounds show cytotoxicity against mouse lymphocytic leukemia cells (L1210) with LD50 values of 2.1

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• temperatures [47][48][49]. Only the CD-HES conjugate 6 did not show any precipitation below 100 °C which was attributed to the much higher hydrophilicity of the anionic carboxylate groups at the HES backbone compared to unmodified HES. Cytotoxicity assays The effect of the CD polymer 5a on the cell viability

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

• new phenolic compound (trogopterin C) were isolated from the crude methanol extract of Trogopterus feces for the first time. The absolute configurations of compounds 1, 2, and 4 were determined by comparing CD spectra and optical rotations. The levels of cytotoxicity against three tumor cell lines (HL

• ', C-2', and C-6'; H-9b→C-1, C-7, C-8, C-1', C-2', and C-6'; H-2'→C-9, C-3', C-4', and C-6'; H-4'→C-2', and C-6'; H-5'→C-1' and C-3', H-6'→C-9, C-2', and C-4'; HREIMS (m/z): calcd for C15H16O3, 244.1099; found, 244.1105. Assessment of cytotoxicity Different types of cancer cells (HL-60, HeLa, and MCF-7

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• (SBECD)) for the formation of inclusion complexes. HPBCD and SBECD showed low cell cytotoxicity in human keratocytes as assessed by the label-free xCELLigence system for real-time monitoring. The fluconazole–HPBCD complex was incorporated into an ion-sensitive ophthalmic gel composed of the natural

• measurement. As shown in Figure 3c, HPBCD induces cytotoxicity immediately after its administration, reaching an initial IC50 value of 40 mg/mL. Subsequently, its value decreases quickly during the exposure period and reaches a stable value of 16 mg/mL after 2.5 hours, which is maintained for over 15 hours

• . This result shows that the cytotoxicity of HPBCD is enhanced with increasing exposure time. In the case of SBECD, cytotoxicity was observed immediately after its addition, reaching an initial IC50 of 22 mg/mL, which is slightly lower than the initial data observed for HPBCD. It then increases gradually