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Antibacterial screenings are most commonly targeted at planktonic bacteria but less effort is dedicated to the exploration of agents acting on biofilms. Here, a natural compounds library was screened against Staphylococcus aureus using a 384-well plate platform to identify compounds preventing biofilm formation. Five structurally diverse hits were selected for follow-up studies: honokiol, tschimganidin, ferutinin, oridonin and deoxyshikonin. The compounds were evaluated against different bacterial species for their capacity to prevent and disrupt biofilms. The development of resistance and cytotoxicity were also investigated. Ferutinin displayed the best antibacterial activity, with a minimum inhibitory, bactericidal and biofilm preventive concentration of 25 mu M against S. aureus. It efficiently disrupted pre-formed biofilms (over 5-log reduction of viable cells) and reduced biofilm formation on a catheter in the presence of neutrophils. This work provides new information on the antibacterial activity of five natural compounds and identified ferutinin as a promising candidate against S. aureus biofilms.

This study aimed to investigate the in vitro cytotoxic activities of orange peel oil on HaCaT cell lines by using an MTT cytotoxicity assay after administering orange peel oil at different doses and time-points. Our objective was to assess the in vitro cytotoxic activities of orange peel oil on HaCaT cell lines.‎ Cell viability was determined with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assays. The HaCaT cells (100 µL) were cultured in plates and treated with different concentrations of orange peel oil (25 µM, 50 µM, 100 µM, 150 µM and 200 µM) for durations of 24 and 48 hours. Cell death was determined by collecting and staining with 0.4% Trypan blue for 5 minutes at room temperature, followed by microscopic examination. There was a significant difference between the doses concerning ‎both time zones (p

In this study, effective and environmentally friendly methods were used to achieve the synthesis of silver nanoparticles (Ag NPs) by an aqueous plant extract. The Ag NPs were synthesized via Zingiber officinale plant extract that acted as a reducing and stabilizing agent. Various techniques, including UV-Visible spectroscopy (UV-Vis), X-ray diffraction pattern (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) were used. The plant extract treated with silver nitrate solution at room temperature (27 ± 20) resulted in the successful synthesis of the Ag NPs, that were confirmed by UV-Vis spectroscopy. The crystalline morphology and size of the nanoparticles were calculated using Scherrer equation, that specify a face-centered cubic (fcc) crystalline structure with size ranges as 16 nm. The spherical geometry of Ag NPs was confirmed from scanning electron microscopy. FT-IR study validates the existence of several functional groups of active biomolecules such as -OH, C-O, C=C, C-O-C, and N-H that act as a reducing and capping agent for the synthesis of Ag NPs and were found in the extract. The synthesized Ag NPs were used to evaluated antimicrobial activity against different bacterial and fungal strains. The Zingiber officinale-Ag NPs exhibited maximum zone of inhibition against Staphylococcus aureus bacterial strain which were 17.8 ± 0.03 mm, and Fusarium graminium fungal strain showed 11.0 ± 0.01 mm at 80 µg/mL concentrations, respectively. Furthermore, the Ag NPs were considered to be a significant anti-asthma agent that decreased the white blood cells (WBC), eosinophils (EOS) in blood level, and wet/dry (W/D) weight proportion of the lung at 24 µg/g/day. The cytotoxicity of synthesized nanoparticles shows that the concentration under 90 µg/mL were biologically compatible.

Sinningia bullata is a tuberous member of the flowering plant family Gesneriaceae. Prior to this work, the antibacterial, antioxidant, and cytotoxic properties of S. bullata were undetermined. Here, we prepared different extracts from the leaf, stem, and tuber of S. bullata and investigated their pharmacological activities. The leaf extract of S. bullata, obtained by 100% acetone (Sb-L-A), had the highest total flavonoid content, antioxidation capacity, and cytotoxic and antibacterial activities. Sb-L-A displayed a broad range of antibacterial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The inhibition zones of Sb-L-A ranged from 8 to 30 mm and were in the following order: S. aureus > E. coli > P. aeruginosa. Incubation of B16F10 melanoma cells with Sb-L-A at a concentration of 80 μg/mL caused deaths at the rate of 96%, reduced migration by 100%, suppressed proliferation and colony formation by 99%, and induced apoptosis, which was observed in 96% of the B16F10 cells. In addition, the cytotoxic activities of Sb-L-A were synergistically enhanced when coacting with the antitumor drug epothilone B. Sb-L-A was also used to determine the cytotoxic effects against 4T1 mammary carcinoma cells. Sb-L-A of 60 μg/mL boosted the distribution of the G2 phase from 1.4% to 24.4% in the B16F10 cells. Accordingly, Sb-L-A might suppress melanoma cell proliferation by inducing G2 cell-cycle arrest. The most abundant compounds in Sb-L-A were identified using gas chromatography–mass spectrometry. The top two contents in this extract were adlupulone and villosin. Overall, the collective data in this study may indicate the pharmacological potentials of Sb-L-A for possible medical applications.

A new aliphatic acid, compound 1, together with six known metabolites, including nonactic acid (2), homononactic acid (3), ethyl homononactate (4), homononactylhomononactate (5), valinomycin (6), and cyclo-(Pro-Leu) (7), was isolated from the culture broth of Streptomyces sp. BM-8, an actinobacterial strain isolated from the feces of Equus quagga. The structures of these compounds were established by analyses of spectroscopic data, including 1D and 2D nuclear magnetic resonance spectra (NMR), as well as by HR-ESI-MS spectrometry and chemical derivative analyses. Additionally, a serial analogue of nonactic acid and homononacticacid (8–21) was synthesized. The cytotoxicity of 1–21 wastested against a panel of cancer cell lines, such as HT-29, MCF-7, A375 and K562, with MTT assay. In addition, the cytotoxicity tests revealed that 1 was less cytotoxic toward a panel of cancerous cells, as compared with valinomycin (6).

Eggplant (Solanum melongena L.) Calyx is a medicinal and edible traditional Chinese medicine with anti-inflammatory, anti-oxidant, and anti-cancer properties. However, the pharmacodynamic components and metabolic characteristics remain unclear. Amide and phenylpropanoid were the two main constituents, and four amides, including n-trans-p-coumaroyltyramine (1), n-trans-p-coumaroyloctopamine (2), n-trans-p-coumaroylnoradrenline (3), n-trans-feruloyloctopamine (4), and a phenylpropanoid neochlorogenic acid (5) were selected. In this study, these five representative compounds showed cytotoxic activities on A549, HCT116, and MCF7 cells. In addition, the metabolites of 1–5 from the eggplant calyx in rats were identified. In total, 23, 37, 29, and 17 metabolites were separately characterized in rat plasma, urine, feces, and livers, by UPLC/ESI/qTOF-MS analysis. The metabolism of amides and phenylpropanoid was mainly involved in hydroxylation, methylation, glucuronidation, or sulfation reactions. Two hydroxylated metabolites (1-M2 and 2-M3) were clearly identified by comparison with reference standards. Rat liver microsome incubation experiments indicated that P450 enzymes could hydroxylate 1–5, and the methylation reaction of the 7-hydroxyl was also observed. This is the first study on the in vivo metabolism of these compounds, which lays a foundation for follow-up studies on pharmacodynamic evaluations and mechanisms.

Overexpression of the histone acetyltransferase and the 1H NMR spectroscopic experiments of the endophytic fungus Monosporascus eutypoides resulted in the isolation of two new compounds, monosporasols A (1) and B (2), and two known compounds, pestaloficin C (3) and arthrinone (4). Their planar structures and absolute configurations were determined by spectroscopic analysis including high resolution electrospray ionization mass spectroscopy (HRESIMS), one-dimensional (1D) and two-dimensional (2D) NMR, and calculated electronic circular dichroism data. Compounds 1–2 were screened in cytotoxic bioassays against HeLa, HCT-8, A549 and MCF-7 cells. Our work highlights the enormous potential of epigenetic manipulation along with the NMR comparison as an effective strategy for unlocking the chemical diversity encoded by fungal genomes.

The chemical investigation of the n-hexane fraction of Salvadora persica L., Salvadoraceae, seeds afforded a new stearic acid ester, salvastearolide, together with five other phytosteroids identified as stigmasterol, β-sitosterol, Δ7-campesterol, Δ7-avenasterol and campesterol. Their structures were established on the basis of extensive spectroscopic methods including 1D and 2D NMR experiments and HRESI mass spectrometry. In addition, salvastearolide and the isolated fractions were tested for their cytotoxicity against human cancer cell lines MCF-7, MDA-MB-231 and HT-29. The n-hexane fraction exhibited significant anti-proliferative effect against human breast cancer cell line MCF-7 (IC50 50 μg/ml), while salvastearolide possessed a weak cytotoxic effect against MCF-7 cells with IC50 103.98 μg/ml. Keywords: Salvastearolide, Phytosteroids, NMR, Cytotoxic activities

Molybdenum(VI) complexes of different nuclearity, mononuclear, [MoO2(L1 or 2) (MeOH)]MeOH (1MeOH and 2MeOH), [MoO2(L1 or 2)(D)] [D = pyridine, (1a and 2a), 3-methylpyridine, (1b and 2b) and 4-methylpyridine, (1c and 2c)], binuclear [{; ; ; ; MoO2(L1 or 2)}; ; ; ; 2(D)] (D = 4, 4'-bipyridine (1d, 1d' and 2d), and polynuclear complexes [MoO2(L1 or 2)]n (3 and 4) were synthesized by solution based reactions of enaminones (H2L1 = 3-(2-hydroxy-4- methylphenylamino)-1-phenylbut-2-en-1-one ; H2L2 = 3-(2- hydroxy-5-methylphenylamino)-1-phenylbut-2-en- 1-one) with the dioxobis(acetylacetonato)molybdenum( VI) complex, [MoO2(acac)2]. Reactions of the mononuclear complexes 1MeOH and 2MeOH with pyridine and its derivatives resulted in corresponding mononuclear [MoO2(L1 or 2)(D)] or binuclear [{; ; ; ; MoO2(L1 or 2)}; ; ; ; 2(D)] complexes. In case of [{; ; ; ; MoO2(L1)}; ; ; ; 2(4, 4-bpy)] two polymorphic forms are obtained (1d and 1d'). The cross-linked transformations of [MoO2(L1 or 2)(D)] complexes in solution or when exposed to vapors of N-heterocyclic bases have been explored. Crystal and molecular structures of ten complexes (1MeOH, 2MeOH, 1a–d, 1d' , 2b–d) were determined by the single-crystal X-ray diffraction analysis. Enaminone ligands and their molybdenum complexes were characterized by elemental and TG analysis, IR and NMR spectroscopy and screened for their in vitro cytotoxic and antibacterial activities. None of the tested compounds showed cytotoxic ability against THP-1 and HepG2 cell lines. Compounds 1MeOH, 1b, 2MeOH, 2a and 3, exhibited weak antibacterial activity on Moraxella catarrhalis strain while other complexes did not show antibacterial properties towards Staphylococcus aureus, Enterococcus faecalis and Escherichia coli bacteria.

Euphorbia grandicornis Blanc is widely utilized in traditional medicine for a variety of ailments including body pains associated with skin irritations, inflammation, and snake or scorpion bites. Compounds from E. grandicornis were characterized using spectroscopic techniques, NMR, IR, MS, and melting points and alongside the extracts were evaluated for in vitro anticancer activity against several cancer cell lines. The root extract afforded known, β-glutinol (1), β-amyrin (2), 24-methylenetirucalla-8-en-3β-ol (3), tirucalla-8,25-diene-3β,24R-diol (4), stigmasterol (5), sitosterol (6), and hexyl (E)-3-(4‑hydroxy-3-methoxyphenyl)-2-propenoate (7) based on their NMR spectroscopic data for the first report in E. grandicornis. The extracts and isolated compounds were evaluated for anticancer activities against hormone receptor-positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12A) cell lines. The CH2Cl2 extract exhibited potent, cytotoxicity against MCF-7, HCC70, and MCF-12A cells. The aerial extract exhibited IC50 values of 1.03, 0.301, and 1.68 µg/mL, and root extract displayed IC50 values of 0.83, 0.83 and 3.98 µg/mL against MCF-7, HCC70, and MCF-12A cells, respectively. The root extract thus showed selectivity for the cancer cell lines over the non-cancerous control cell line (SI = 4.80). Hexyl (E)-3-(4‑hydroxy-3-methoxyphenyl)-2-propenoate (7) showed significant activity with IC50 values of 23.41, 29.45 and 27.01 µM against MCF-7, HCC70 and MCF-12A cells, respectively, suggesting non-specific cytotoxicity.

In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol (

Five new anthraquinone derivatives, auxarthrols D–H (1–5), along with two known analogues (6–7), were obtained from the culture of the marine-derived fungus Sporendonema casei. Their structures, including absolute configurations, were established on the basis of NMR, HRESIMS, and circular dichroism (CD) spectroscopic techniques. Among them, compound 4 represents the second isolated anthraquinone derivative with a chlorine atom, which, with compound 6, are the first reported anthraquinone derivatives with anticoagulant activity. Compounds 1 and 3 showed cytotoxic activities with IC50 values from 4.5 μM to 22.9 μM, while compounds 1, 3–4, and 6–7 showed promising antibacterial activities with MIC values from 12.5 μM to 200 μM. In addition, compound 7 was discovered to display potential antitubercular activity for the first time.

Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. Two new withanolides (1–2), together with six known analogues (3–8), were isolated from the whole plant of Physalis angulata L. The structures of these new compounds were determined on the basis of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The withanolides exhibited strong cytotoxic activities against A549, Hela and p388 cell lines. Furthermore, compounds 1 and 2 induced typical apoptotic cell death in A549 cell line according to the evaluation of the apoptosis-inducing activity by flow cytometric analysis.

WOS: 000397052800016, PubMed ID: 27793449, Abietic and dehydroabietic acid are interesting diterpenes with a highly diverse repertoire of associated bioactivities. They have, among others, shown antibacterial and antifungal activity, potentially valuable in the struggle against the increasing antimicrobial resistance and imminent antibiotic shortage. In this paper, we describe the synthesis of a set of 9 abietic and dehydroabietic acid derivatives containing amino acid side chains and their in vitro antimicrobial profiling against a panel of human pathogenic microbial strains. Furthermore, their in vitro cytotoxicity against mammalian cells was evaluated. The experimental results showed that the most promising compound was 10 [methyl N-(abiet-8,11, 13-trien-18-yl)-D-serinate], with an MIC90 of 60 mu g/mL against Staphylococcus aureus ATCC 25923, and 8 mu g/mL against methicillin-resistant S. aureus, Staphylococcus epidermidis and Streptococcus mitis. The IC50 value for compound 10 against Balb/c 3T3 cells was 45 mu g/mL, European Union Programme FP7 WoodWisdom-Net+ under Academy of Finland [256515]; TUBITAK [110O951]; Academy of Finland [277001, 284477, 264020, 265481]; Magnus Ehrnrooth Foundation [ME2012n44], This work was supported by the European Union Seventh Framework Programme FP7 WoodWisdom-Net+ under Academy of Finland grant agreement no. 256515 (GREASE) and TUBITAK 110O951. A.H. and P.T. (Grant nos. 277001 and 284477) and J.Y. K. (Grants nos. 264020 and 265481) were also supported by the Academy of Finland. V.M.M. thanks the Magnus Ehrnrooth Foundation (project ME2012n44) for financial support.

A series of novel N9-heterobivalent β-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC50 value of lower than 20 μM. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 5b and 5w exhibited that tumour inhibition rate of over 40% in the Sarcoma 180 and Lewis lung cancer animal models. Preliminary structure–activity relationships (SARs) analysis indicated that: (1) C1-methylation and C7-methoxylation were favorable for increased activities; (2) 3-Pyridyl or 2-thienyl group substituent into position-1 of the β-carboline core, and the aryl substituent into another β-carboline ring might be detrimental to cytotoxic effects of this class compounds. Investigation of the preliminary mechanism of action demonstrated that compound 5b had obvious angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM) assay.

Pot marigold (Calendula officinalis L.) is native to southern Europe. Compounds of marigold flowers exhibit anti-inflammatory, anti-tumor-promoting, and cytotoxic activities (4). In Serbia, pot marigold is cultivated as an important medicinal and ornamental plant. Typical phyllody, virescence, proliferation of axillary buds, and witches' broom symptoms were sporadically observed in 2011 in Pancevo plantation, Serbia (44°51′49″ N, 20°39′33″ E, 80 m above sea level). Until 2013, the number of uniformly distributed affected pot marigold plants reached 20% in the field. Due to the lack of seed production, profitability of the cultivation was seriously affected. Leaf samples from 10 symptomatic and 4 symptomless marigold plants were collected and total nucleic acid was extracted from midrib tissue (3). Direct PCR and nested PCR were carried out with primer pairs P1/16S-SR and R16F2n/R16R2n, respectively (3). Amplicons 1.5 and 1.2 kb in length, specific for the 16S rRNA gene, were amplified in all symptomatic plants. No PCR products were obtained when DNA isolated from symptomless plants was used. Restriction fragment length polymorphism (RFLP) patterns of the 1.2-kb fragments of 16S rDNA were determined by digestion with four endonucleases separately (TruI1, AluI, HpaII, and HhaI) and compared with those of Stolbur (Stol), Aster Yellows (AY), Flavescence dorée-C (FD-C), Poinsettia Branch-Inducing (PoiBI), and Clover Yellow Edge (CYE) phytoplasmas (2). RFLP patterns from all symptomatic pot marigold plants were identical to the Stol pattern, indicating Stolbur phytoplasma presence in affected plants. The 1.2-kb amplicon of representative Nv8 strain was sequenced and the data were submitted to GenBank (accession no. KJ174507). BLASTn analysis of the sequence was compared with sequences available in GenBank, showing 100% identity with 16S rRNA gene of strains from Paeonia tenuifolia (KF614623) and corn (JQ730750) from Serbia, and peach (KF263684) from Iran. All of these are members of the 16SrXII ‘Candidatus Phytoplasma solani’ group, subgroup A (Stolbur). Phytoplasmas belonging to aster yellows (16SrI) (Italy and Canada) and peanut witches' broom related phytoplasma (16SrII) group (Iran) have been identified in diseased pot marigold plants (1). To our knowledge, this is the first report of natural infection of pot marigold by Stolbur phytoplasma in Serbia. References: (1) S. A. Esmailzadeh-Hosseini et al. Bull. Insectol. 64:S109, 2011. (2) I. M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (3) J. P. Prince. Phytopathology 83:1130, 1993. (4) M. Ukiya et al. J. Nat. Prod. 69:1692, 2006.

Eryngium campestre and E. amethystinum are thorny herbs belonging to the Apiaceae family and spontaneously growing in stony pastures and dry meadows, preferentially on calcareous substrates. In the Mediterranean countries, these plants have been used as a food or traditional remedies to treat various ailments. In the present work, we have analysed the chemical composition of the essential oils distilled from the aerial parts by GC-FID and GC-MS, and evaluated their cytotoxic effects on a panel of human cancer cells, namely A375 (human malignant melanoma), MDA-MB 231 cells (human breast adenocarcinoma) and HCT116 cells (human colon carcinoma), by the MTT assay. Furthermore, the Eryngium essential oils were evaluated for antioxidant and acetylcholinesterase (AChE) activities. The two essential oils were rich in sesquiterpene hydrocarbons, with germacrene D as the major compound, accompanied by allo-aromadendrene, β-elemene, spathulenol and ledol. They resulted highly cytotoxic on the tumor cells, with IC50 values (1.65-5.32 and 1.57-2.99 μg/ml for E. amethystinum and E. campestre, respectively) comparable or close to those of the anticancer drug cisplatin. The E. amethystinum essential oil exhibited a moderate antioxidant activity whereas that of E. campestre a weak AChE inhibition. This article is protected by copyright. All rights reserved.

Phytochemical investigation of EtOAc extract from the stem bark of Berlinia confusa yielded a new and two known polysaturated monoacylglycerides characterised as 1- O -docosanoyl-sn-glyceride ( 3 ), 1- O -(13-methyltetradecanoyl)-sn-glycerol ( 4 ) and 1- O -pentadecacanoyl-sn-glycerol ( 5) ; along with the known compounds betulinic acid ( 1 ) and sitosteryl-β- d -glucoside ( 2 ). The structures of these compounds were elucidated using analytical methods, including 1D and 2D-NMR together with MS spectroscopy. The extracts and isolated compounds demonstrated concentration-dependent anthelmintic activities against Fusciola gigantica (liver flukes) and Taenia solium (tapeworm) at 10–100 mg/ml. The extracts and isolated compounds were evaluated for cytotoxicity against a small panel of three human tumour cell lines.

Objective: To prepare different polarities leave crude extracts of Juniperus excels (J. excels) and to determine their phytochemical screening, antioxidant, antimicrobial and cytotoxic activities. Methods: The phytochemical screening of different crude extracts was determined by well-established methods. The antioxidant activity was determined by free radical scavenging (2,2-diphenyl-1-picrylhydrazyl, DPPH) method. The antimicrobial activity was evaluated by agar disc diffusion method and cytotoxic activity was determined through brine shrimp lethality assay. Results: The phytochemical tests showed that alkaloids, flavonoids, saponins, steroide, triterpenoids and tannins are present in all leave crude extracts except chloroform crude extract do not contain tannins. The antioxidant results of crude extracts were found to be in the order of hydro alcoholic > chloroform> ethyl acetate >hexane. All leave crude extracts showed moderate antibacterial against gram positive and gram negative food borne pathogen bacteria. The cytotoxicity results revealed that hexane and chloroform extracts have killed all the shrimp larvae at the concentration of 500 μg/mL. Conclusion: More in-vivo and in-vitro studies along with detailed phytochemical investigations are needed in order to potentially use this plant in the prevention and therapies of some oxidative damage related diseases.

The chemical examination of the solid cultures of the deep-sea-derived fungus Penicillium chrysogenum MCCC 3A00292 resulted in the isolation of three new versiol-type analogues, namely peniciversiols A–C (1–3), and two novel lactone derivatives, namely penicilactones A and B (6 and 7), along with 11 known polyketides. The planar structures of the new compounds were determined by the comprehensive analyses of the high-resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) data, while their absolute configurations were resolved on the basis of comparisons of the experimental electronic circular dichroism (ECD) spectra with the calculated ECD data. Compound 1 is the second example of versiols featuring a 2,3-dihydropyran-4-one ring. Additionally, compounds 6 and 7 are the first representatives of γ-lactone derivatives constructed by a 1,3-dihydroxy-5-methylbenzene unit esterifying with the α-methyl-γ-hydroxy-γ-acetic acid α,β-unsaturated-γ-lactone moiety and α-hydroxy-γ-methyl-γ-acetic acid α,β-unsaturated-γ-lactone unit, respectively. All of the isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines of BIU-87, ECA109, BEL-7402, PANC-1, and Hela-S3. Compound 1 exhibited a selective inhibitory effect against the BIU-87 cell line (IC50 = 10.21 μM), while compounds 4, 5, 8, and 12–16 showed inhibitory activities against the ECA109, BIU-87, and BEL-7402 cell lines with the IC50 values ranging from 7.70 to &gt, 20 μM.

Five new anthraquinone derivatives, auxarthrols D&ndash, H (1&ndash, 5), along with two known analogues (6&ndash, 7), were obtained from the culture of the marine-derived fungus Sporendonema casei. Their structures, including absolute configurations, were established on the basis of NMR, HRESIMS, and circular dichroism (CD) spectroscopic techniques. Among them, compound 4 represents the second isolated anthraquinone derivative with a chlorine atom, which, with compound 6, are the first reported anthraquinone derivatives with anticoagulant activity. Compounds 1 and 3 showed cytotoxic activities with IC50 values from 4.5 &mu, M to 22.9 &mu, M, while compounds 1, 3&ndash, 4, and 6&ndash, 7 showed promising antibacterial activities with MIC values from 12.5 &mu, M to 200 &mu, M. In addition, compound 7 was discovered to display potential antitubercular activity for the first time.

Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat C-9, C-13, and C-14. The daphnane-type diterpenoids can be classified into five types: 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the oxygen-containing functions at rings B and C, as well as the substitution pattern of ring A. Up to now, nearly 200 daphnane-type diterpenoids have been isolated and elucidated from the Thymelaeaceae and Euphorbiaceae families. In-vitro and in-vivo experiments of these compounds have shown that they possess a wide range of biological activities, including anti-HIV, anti-cancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. A comprehensive account of the structural diversity is given in this review, along with the cytotoxic activities of daphnane-type diterpenoids, up to April 2019.

The study evaluated the antitumor activity of tylopilan, aβ- (1→3) (1→6) linked glucan isolated from fruiting bodies of Tylopilus felleus (Bull.: Fr.) P. Karst. (Boletaceae), and Propionibacterium acnes (P.a.) preparation. The antitumor effect of tylopilan and P.a. used alone or in combination was studied in NMRI mice inoculated i.p. with 106 180-TG Crocker tumor cells. All experiments were based on a pretreatment with tylopilan and/or P.a. 5 days and/or 2 h before tumor cell inoculation. Mean survival time (MST) of tumor - bearing mice was significantly prolonged in comparison to control mice by a single injection of tylopilan (25 µg/mouse or 50 µg/mouse) or P.a. (1 mg/mouse). MST was 23.6; 22.8 days in the tylopilan injected mice and 17.5 in the control animals. Tylopilan injected in conjunction with P.a. prolonged signifi-cantly MST in comparison to control mice as well as to tylopilan alone treated mice. We have found that P.a. which stimulate immune response enhanced significantly antitumor activity of tylopilan. The cytotoxicity of tylopilan at concentrations of 300, 150, 75 and 37.5 µg/ml towards 180-TG Crocker cells in vitro studies was evaluated. All examined tylopilan concentrations showed cytotoxic activity.

A small series of 1-acetyl-2-(4-alkoxy-3-methoxyphenyl)cyclopropanes was prepared, starting from dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one) and its O-alkyl derivatives. Their microbiological activities toward some strains of bacteria and fungi were tested, as well as their in vitro cytotoxic activity against some cancer cell lines (HeLa, LS174 and A549). All synthesized compounds showed significant antimicrobial activity and expressed cytotoxic activity against tested carcinoma cell lines, but they showed no significant influence on normal cell line (MRC5). Butyl derivative is the most active on HeLa cells (IC50 = 8.63 μm), while benzyl one is active against LS174 and A549 cell lines (IC50 = 10.17 and 12.15 μm, respectively).

Centaurea ragusina L., an endemic Croatian plant species, revealed a good cytotoxic activity of aqueous extracts (AE) on human bladder (T24) and human glioblastoma (A1235) cancer cell lines. The chemical constituents were tentatively identified using high performance liquid chromatography HPLC-DAD/ ESI-TOF-MS in negative ionization mode. The main compounds of herba extract were sesquiterpene lactones: solstitialin A 3,13-diacetate and epoxyrepdiolide; organic acid: quinic acid. The main compounds of flower extract were organic acids: quinic acid, citric acid, and malic acid; sesquiterpene lactone: cynaropicrin; phenolic compounds: chlorogenic acid and phenylpropanoid: syringin. The AE of C. ragusina were investigated for correlation of their effects on human bladder (T24) and human glioblastoma (A1235) cancer cell lines using the MTT assay. Although both extracts showed significant dose-and time-dependent cytotoxic activity against both cancer cell lines, the flower extract exhibited slightly higher activity. In order to determine type of cell death induced by treatment, cell lines were exposed subsequently to a treatment with both flower and herba AE. The majority of the cells died by induced apoptosis treatment. Flower AE (26.25%), compared to a leaf AE (22.15%) showed slightly higher percentage of an apoptosis in T24 cells, when compared to a non-treated cells (0.04%). This is the peer-reviewed version of the following article: Radan, M.; Carev, I.; Tešević, V.; Politeo, O.; Čulić, V. Č. Qualitative HPLC-DAD/ESI-TOF-MS Analysis, Cytotoxic, and Apoptotic Effects of Croatian Endemic Centaurea Ragusina L. Aqueous Extracts. Chemistry and Biodiversity 2017, 14 (9). [https://doi.org/10.1002/cbdv.201700099]

The marine fungus Chondrostereum sp. was collected from a soft coral of the species Sarcophyton tortuosum from the South China Sea. Three new compounds, chondrosterins F–H (1, 4 and 5), together with three known compounds, incarnal (2), arthrosporone (3), and (2E)-decene-4,6,8-triyn-1-ol (6), were isolated. Their structures were elucidated primarily based on NMR and MS data. Incarnal (2) exhibited potent cytotoxic activity against various cancer cell lines.

Background Ptycholobium is a genus related to Tephrosia which comprises only three species. Compared to Tephrosia, which has been phytochemically and pharmacologically studied, Ptycholobium species have only few or no reports on their chemical constituents. Moreover, no studies on the cytotoxic activities of its secondary metabolites have been previously documented. Results From the non polar fractions of the roots bark of Ptycholobium contortum (syn Tephrosia contorta), two new pterocarpans: seputhecarpan C 1 and seputhecarpan D 2 and a new pyrone derivative, ptycholopyrone A 3 were isolated. Alongside, five known compounds identified as 3-α,α-dimethylallyl-4-methoxy-6-styryl-α-pyrone or mundulea lactone 4, glyasperin F 5, seputhecarpan A 6, seputheisoflavone 7 and 5-O-methyl-myo-inositol or sequoyitol 8 were also obtained. Their structures were established by the mean means of spectroscopic data in conjunction to those reported in literature. The NMR assignment of the major compound mundulea lactone 4 is revised in this paper. In addition, the cytotoxicity of the isolated metabolites was evaluated on two lung cancer cell lines A549 and SPC212. 8 was not active while compounds 1, 2, 4–7 displayed antiproliferative effects against the two carcinoma cell lines with IC50 values below 75 µM. IC50 values below 10 µM were obtained for 4, 6 and 7 on SPC212 cells. Conclusion Based on the obtained results, Ptycholobium contortum turns to be a rich source of phenolic metabolites among them some bearing prenyl moieties. This study reports for the first time the isolation of pyrone derivatives 3 and 4 from Ptycholobium genus. The cytotoxicity observed for the isolate is also reported for the first time and shows that 4, 6 and 7 could be chemically explored in order to develop a hit candidate against lung cancer. Graphical abstract Two new pterocarpans and a new pyrone derivative with cytotoxic activities from ptycholobium contortum (N.E.Br.) Brummitt (Leguminosae): revised NMR assignment of mundulea lactone. Electronic supplementary material The online version of this article (doi:10.1186/s13065-016-0204-x) contains supplementary material, which is available to authorized users.

Four sesterterpenes, erectusolides B, C, D, and seco-manoalide-25-methyl ether, two 2-furanone derivatives, erectusfuranones A and B, together with thirteen known sesterterpenes, (6Z)-neomanoalide-24-acetate, two diastereomers of 24-O-methylmanoalide, luffariolide B, manoalide, (6E)- and (6Z)-neomanoalide, seco-manoalide, scalarafuran, 12-acetylscalarolide, 12-epi-O-deacetyl-19-deoxyscalarin, 12-epi-scalarin, and 12-O-deacetyl-12-epi-scalarin, three indole alkaloids, 5-hydroxy-1H-indole-3-carbaldehyde, hyrtiosine A, and variabine B, and one norterpene, cavernosine were isolated from the marine sponge Hyrtios erectus. Their structures were determined by means of spectroscopic methods and the absolute configurations of the asymmetric centers were determined using the modified Mosher’s method. The cytotoxic activities for the isolated compounds have been reported.

Immunotoxins are fusion proteins of modified toxin conjugated to tumor cell selective ligand. Denileukin diftitox approved by FDA for treatment of CTCL is diphtheria toxin (DT)/IL2 fusion protein targeted to high affinity IL2R. Here, we have attempted to target the more uniquely expressed low affinity IL2R (IL2R?). We designed four immunotoxins, SPRSV1 was designed to code for a single protein of DT (390) and IL2 (133) without any extra amino acids at the junction. SPRSV2 was designed to selectively target low affinity IL2R, it codes for DT (390) and IL2 (69). We also constructed SPRSV3 encoding for only DT (390) without any ligand, as negative control and SPRSV4 was designed similar to commercial equivalent denileukin diftitox, it codes for DT (387) and IL2 (133) with His at the junction. The cytotoxic activities of these immunotoxins were tested in various cell lines, cell lines lacking IL2R expression and healthy MNC were used as controls. The activities of SPRSV1 and SPRSV2 were comparable to that of SPRSV4. SPRSV2 exhibited potent cytotoxicity effectively targeted to ? subunit of IL2R on various leukemia cell lines. Our studies also showed a negative correlation between CD25 expression and percentage cell viability after treatment with immunotoxins. � 2010 Elsevier B.V.

Complexes [Au(PyCT4BrPh)Cl]Cl (1), [Pt(PyCT4BrPh)Cl]0.5KCl (2), and [Pd(PyCT4BrPh)Cl]KCl (3) were obtained with 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh). Although complexes (2) and (3) did not exhibit potent cytotoxic activity, HPyCT4BrPh and its gold(III) complex (1) proved to be highly cytotoxic against HL-60 (human promyelocytic leukemia) and THP-1 (human monocytic leukemia) cells, and against MDA-MB 231 and MCF-7 (human breast adenocarcinoma) solid tumor cells. Except for HL-60 cells, upon coordination to gold(III) a 2- to 3-fold increase in the cytotoxic effect was observed. An investigation on the possible biological targets of the gold(III) complex was carried out. Complex (1) but not the free thiosemicarbazone inhibits the enzymatic activity of thioredoxin reductase (TrxR). The affinity of 1 for TrxR suggests metal binding to a selenol residue in the active site of the enzyme. While HPyCT4BrPh was inactive, 1 was able to inhibit topoisomerase IB (Topo IB) activity. Hence, inhibition of TrxR and Topo IB could contribute to the mechanism of cytotoxic action of complex (1).

A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide–alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via the reaction of aryl amine (obtained from nimesulide) with α-chloroacetyl chloride followed by displacing the α-chloro group by an azide. Some of the synthesized compounds showed encouraging PDE4B inhibitory properties in vitro that is >50% inhibition at 30 μM that were supported by the docking studies of these compounds at the active site of PDE4B enzyme (dock scores ∼ −28.6 for a representative compound). Two of these PDE4 inhibitors showed promising cytotoxic properties against HCT-15 human colon cancer cells in vitro with IC50 ∼ 21–22 μg/mL.

Background Zanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used in traditional system of medicine for diarrhea, pain, wound healing, etc. in Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its bioactive compounds whereas the investigation on Z. zanthoxyloides fruits is lacking. Results After a detailed chemical analysis of the fruits of Z. leprieurii and Z. zanthoxyloides, a series of new acridone alkaloids, namely, 3-hydroxy-1,5,6-trimethoxy-9-acridone (1), 1,6-dihydroxy-3-methoxy-9-acridone (2), 3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone (3), 4-methoxyzanthacridone (8), 4-hydroxyzanthacridone (9), 4-hydroxyzanthacridone oxide (2,4’) (10) have been isolated. The known acridones which have been characterized are, helebelicine A (4), 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), 1,3-dihydroxy-4-methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). The in vitro antibacterial and cytotoxic screening of these acridones reveal that compound 3 has a moderate antibacterial activity (MIC 125 μg/mL) against Micrococcus luteus and Pseudomonas aeruginosa while compound 1 shows a moderate cytotoxic effect (IC50 of 86 μM) against WRL-68 (liver cancer cell line). Furthermore, the molecular modeling of these acridones predicted the structural basis for their mode of action and binding affinity for aromatase, quinone reductase and WAAG, a glycosyltransferase involved in bacterial lipopolysaccharide synthesis. Computational approaches, quantitative SAR and modeling studies predicted that acridones 1, 2, 3, 4, 9 and 10 were the inhibitors of glycosyltransferase while 1, 8, 9 and 10, the inhibitors of aromatase. Conclusions A total of 10 acridones have been isolated out of which 6 are new (1, 2, 3, 8, 9 and 10). Alkaloids 8, 9 and 10, having novel tetracyclic acridone structure with new carbon skeleton, have now been named as zanthacridone. The quantitative SAR and molecular modeling studies suggested that the compounds 1, 9 and 10 are inhibitors of both aromatase and glycosyltransferase.

Two edible plants in Southeast Asia, Gynura bicolor and G.divaricata, are not only known to be nutritive but also useful as medicinal herbs. Previous phytochemical investigation of Gynura species showed the presence of hepatotoxic pyrrolizidine alkaloids (PAs), indicating the toxic risk of using these two plants. The present study was designed to analyze the distribution of PA components and tried to evaluate the preliminary toxicity of these two Gynura species. Eight samples of G.bicolor and G.divaricata from five different Chinese locations were collected and their specific PAs were qualitatively characterized by applying an UPLC/MS/MS spectrometry method. Using a pre-column derivatization HPLC method, the total retronecine ester-type PAs in their alkaloids extracts were quantitatively estimated as well. Finally, their genotoxicity was investigated with an effective high-throughput screening method referred to as Vitotox test and their potential cytotoxicity was tested on HepG2 cells. It was found that different types of PAs were widely present in Gynura species collected from south of China. Among them, no significant genotoxic effects were detected with serial concentrations through the present invitro assay. However, the cytotoxicity assay of Gynura plants collected from Jiangsu displayed weak activity at the concentration of 100mg/ml. It is important to note that this research validates in part the indication that the use of Gynura species requires caution.

Four new organotin(iv) complexes of bis-(2,6-di-tert-butylphenol)tin(iv) dichloride [(tert-Bu-)2(HO-Ph)]2SnCl2 (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl- pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)2(HO-Ph)]2Sn(PMT) 2} (2), {[(tert-Bu-)2(HO-Ph)]2Sn(MPMT) 2} (3), {[(tert-Bu-)2(HO-Ph)]2SnCl(PYT)} (4) and {[(tert-Bu-)2(HO-Ph)]2SnCl(MBZT)} (5), have been synthesized and characterized by elemental analysis, 1H-, 13C-, 119Sn-NMR, EPR, FT-IR, Raman and Mössbauer spectroscopic techniques. The crystal and molecular structures of compounds 1-5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1-5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(iv) with trans-C2, cis-N2, cis-S2-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(iv) cation. Compounds 1-5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC50 = 0.58 ± 0.1 μM). © 2012 The Royal Society of Chemistry. 41 48 14568 14582 Cited By :24

Two new O-prenylated acridone alkaloids, balsacridone A (1) and B (2), together with eighteen known compounds were isolated from the methanol extract from the stems of Balsamocitrus paniculata, a Cameroonian medicinal plant. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, and chemical reactions. N-methyl-6-methoxybenzoxazolinone (16) was isolated for the first time from a natural source while compounds 13, 14, and 15 for the first time from this genus. Pure compounds were tested for their activity against bacteria, fungi, and plant pathogen oomycetes, using the paper disk agar diffusion assay. The agar diffusion test delivered low to missing antimicrobial activities, corresponding to MICs > 1 mg/mL. However, compounds 1-15 exhibited a strong suppressive effect on phagocytosis response upon activation with serum opsonized zymosan in the range of IC(50) = 0.5-7.2 mu M, and the acridone alkaloids (1-5), N-trans- p-coumaroyltyramine (13), and N-trans-p-coumaroyloctopamine (14) displayed weak cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC(50) values ranging from 69.8 to 99.0 mu M.

Two novel cytotoxic and antifungal constituents, (4S,6S)-6-[(1S,2R)-1, 2-dihydroxybutyl]-4-hydroxy-4-methoxytetrahydro-2H-pyran-2-one (1), (6S,2E)-6-hydroxy-3-methoxy-5-oxodec-2-enoic acid (2), together with three known compounds, LL-P880γ (3), LL-P880α (4), and Ergosta-5,7,22-trien-3b-ol (5) were isolated from the metabolites of endophytic fungi from Dendrobium officinale. The chemical structures were determined based on spectroscopic methods. All the isolated compounds 1–5 were evaluated by cytotoxicity and antifungal effects. Our present results indicated that compounds 1–4 showed notable anti-fungal activities (minimal inhibitory concentration (MIC) ≤ 50 μg/mL) for all the tested pathogens including Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, Aspergillus fumigatus. In addition, compounds 1–4 possessed notable cytotoxcities against human cancer cell lines of HL-60 cells with the IC50 values of below 100 μM. Besides, compounds 1, 2, 4 and 5 showed strong cytotoxities on the LOVO cell line with the IC50 values were lower than 100 μM. In conclusion, our study suggested that endophytic fungi of D. officinale are great potential resources to discover novel agents for preventing or treating pathogens and tumors.

The preparation of several new truncated analogues of the natural dihydropyrone pironetin is described. They differ from the natural product mainly in the suppression of some of the alkyl pendants in either the side chain or the dihydropyrone ring. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that all analogues are cytotoxic towards two either sensitive or resistant tumoral cell lines with similar IC50 values in each case, thus strongly suggesting that, like natural pironetin, they also display a covalent mechanism of action. Their cytotoxicity is, however, lower than that of the parent compound. This indicates that all alkyl pendants are necessary for the full biological activity, with the ethyl group at C-4 seemingly being particularly relevant. Most likely, the alkyl groups cause a restriction in the conformational mobility of the molecule and reduce the number of available conformations. This makes it more probable that the molecule preferentially adopts a shape which fits better into the binding point in α-tubulin., Financial support has been granted to M. C. by the Spanish Government (Ministerio de Economía y Competitividad, project numbers CTQ2008-02800 and CTQ2011-27560), by the Consellería d’Empresa, Universitat i Ciencia de la Generalitat Valenciana (projects ACOMP09/113 and PROMETEO/2013/027) and by the Universitat Jaume I (projects P1-1B-2008-14 and PI-1B-2011-37). The biological work has been supported in part by grants from the Spanish Ministry of Education and Science (grant number BIO2010-16351) and from the Comunidad de Madrid (grant number S2010/BMD-2457 BIPEDD2- CM), both to J. F. D. We thank Dr I. López Martín for her help with part of the experimental synthetic work. We further thank the Matadero Municipal Vicente de Lucas in Segovia for providing the calf brains, which were the source of tubulin. J. A. M. thanks the COST Action CM0804 for help in establishing cooperation with other research groups

[EN] Combined chemo and photothermal therapy in in vitro testing has been achieved by means of multifunctional nanoparticles formed by plasmonic gold nanoclusters with a protecting shell of porous silica that contains an antitumor drug. We propose a therapeutic nanoplatform that associates the optical activity of small gold nanoparticles aggregates with the cytotoxic activity of 20(S)-camptothecin simultaneously released for the efficient destruction of cancer cells. For this purpose, a method was used for the controlled assembly of gold nanoparticles into stable clusters with a tailored absorption crosssection in the vis/NIR spectrum, which involves aggregation in alkaline medium of 15 nm diameter gold colloids protected with a thin silica layer. Clusters were further encapsulated in an ordered homogeneous mesoporous silica coating that provides biocompatibility and stability in physiological fluids. After internalization in 42-MG-BA human glioma cells, these protected gold nanoclusters were able to produce effective photothermolysis under femtosecond pulse laser irradiation of 790 nm. Cell death occurred by combination of a thermal mechanism and mechanical disruption of the membrane cell due to induced generation of micrometer-scale bubbles by vaporizing the water inside the channels of the mesoporous silica coating. Moreover, the incorporation of 20(S)-camptothecin within the pores of the external shell, which was released during the process, provoked significant cell death increase. This therapeutic model could be of interest for application in the treatment and suppression of non-solid tumors., This work was financially supported by Comision Interministerial de Ciencia y Tecnologia of Spain through the projects FIS2006-09319, SAF2008-03694, MAT2006-14274-C02-01 and MULTICAT (Consolider-Ingenio 2010). CM thanks the Spanish "Ministerio de Economia y Competitividad" for a FDU Ph D studentship (AP2008-02851).