Phenylethanoid glycosides from Scutellaria galericulata

From the aerial parts of Scutellaria galericulata L., four phenylethanoid glycosides, 2-(4-hydroxyphenyl)-ethyl-(6-O-caffeoyl)-\beta -D-glucopyranoside (1), calceolarioside B (2), osmanthuside E (3) and martynoside (4), were isolated. The structure elucidations of the isolated compounds were performed by spectroscopic (UV, IR, ESI-MS, 1D- and 2D-NMR) methods. Compounds 1-4 demonstrated scavenging properties toward the 1,1-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC autographic assays

Cytotoxic bromoindole derivatives and terpenes from the Philippine marine sponge Smenospongia sp.

A detailed chemical analysis of a Philippine marine sponge Smenospongia sp. has been performed. This study yielded four new metabolites, 5-bromo-l-tryptophan (1), 5-bromoabrine (2), 5,6-dibromoabrine (3) and 5-bromoindole-3-acetic acid (4). The pyrroloiminoquinone alkaloid, makaluvamine O (5) as well as 5,6-dibromotryptamine (6), aureol (7) and furospinulosin 1 (8) were also isolated. Although 1 and 4 have been synthesized previously, this is the first report on the isolation of these compounds from a natural source. The furanosesterterpene furospinulosin 1 (8) was obtained for the first time from the genus Smenospongia. The structures of all compounds were established by spectroscopic methods (UV, IR, 1D and 2D NMR, MS, [α]D). The cytotoxic potential of 1Ð8 was evaluated in a panel of isogenic HCT-116 human colon tumor cell lines

Analysis of the volatile components of five Turkish Rhododendron species by headspace solid-phase microextraction and GC-MS (HS-SPME-GC-MS)

Volatile constituents of various solvent extracts (n-hexane, CH2Cl2, H2O) of 15 different organs (leaves, flowers, fruits) of five Rhododendron species (Ericaceae) growing in Turkey were trapped with headspace solid-phase microextraction (HS-SPME) technique and analyzed by GC-MS. A total of 200 compounds were detected and identified from organic extracts, while the water extracts contained only traces of few volatiles. The CH2Cl2 extract of the R. luteum flowers was found to exhibit the most diverse composition: 34 compounds were identified, with benzyl alcohol (16.6%), limonene (14.6%) and p-cymene (8.4%) being the major compounds. The CH2Cl2-solubles of R. x sochadzeae leaves contained only phenyl ethyl alcohol. This study indicated appreciable intra-specific variations in volatile compositions within the genus. Different anatomical parts also showed altered volatile profiles. This is the first application of HS-SPME-GC-MS on the volatiles of Rhododendron species

Rapid chemical analysis and antiprotozoal effect of the solvent extracts and the essential oil of Artemisia indica

Artemisia indica is used as antipyretic in malarial fevers during malaria outbreaks in India [1]. We selected this plant because reports concerning the presence of artemisinin is contradictory, the content of methoxyflavonoids that potentiate the antimalarial efficacy of artemisinin has remained unstudied and the essential oil of the plant from different regions shows great chemical variations. Solvent extracts [petroleum ether, n-hexane, dichloromethane, acetone, MeOH or EtOH (96, 80 or 60% v/v), and hot water] of A. indica leaves originated from the West Bengal region (India) were assessed by HPLC-DAD and HPLC-MS for the content of artemisinin and the characteristic Artemisia methoxyflavonoids, eupatin, casticin, chrysoplenetin, cirsilineol, chrysosphenol-D and artemetin. None of the extracts contained artemisinin or the methoxyflavonoids chrysosphenol-D and artemetin, while all extracts contained chrysoplenetin. Eupatin, casticin and cirsilineol were found in all extracts except for the p. ether, n-hexane and hot water infusion. The acetone and EtOH extracts contained the highest levels of polymethoxyflavonoids (1.15 – 1.17%), whereas the infusion was devoid of them. The essential oil of the plant was obtained by hydrodistillation and analyzed by GC and GC-MS simultaneously. Of the 92 compounds detected in the oil, camphor (13.0%) and caryophyllene oxide (10.87%) were the major components. All solvent extracts and the volatile oil showed in vitro antimalarial activity (1.8 – 20 µg/mL). Except for the infusion, all extracts were also active against other parasitic protozoa (Trypanosoma b. rhodesiense, T. cruzi, Leishmania donovani). This is the first study investigating both artemisinin and polymethoxyflavonoid content and detailed in vitro antiprotozoal potential of A. indica extracts and the essential oil

Bisabolane type sesquiterpenes from a marine Didiscus sponge

Two bisabolane type sesquiterpene phenols, (+)-curcuphenol (1) and (+)-curcudiol (2), were isolated from a Philippine marine sponge, Didiscus sp., in addition to b -sitosterol (3) and phenethylamine (4). The structures of the metabolites were established on the basis of spectral evidence (1D- and 2D NMR, [a]D, EIMS). (+)-Curcuphenol (1) showed cytotoxicity, which is indicative of a p53 independent mechanism

Synthesis and antitrypanosomal activities of novel pyridylchalcones

Collaboration with the London School of Hygiene and Tropical Medicine. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.A library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC50 value of 0.29 M. Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT)

Glial wingless/Wnt regulates glutamate receptor clustering and synaptic physiology at the Drosophila neuromuscular junction

Glial cells are emerging as important regulators of synapse formation, maturation, and plasticity through the release of secreted signaling molecules. Here we use chromatin immunoprecipitation along with Drosophila genomic tiling arrays to define potential targets of the glial transcription factor Reversed polarity (Repo). Unexpectedly, we identified wingless (wg), a secreted morphogen that regulates synaptic growth at the Drosophila larval neuromuscular junction (NMJ), as a potential Repo target gene. We demonstrate that Repo regulates wg expression in vivo and that local glial cells secrete Wg at the NMJ to regulate glutamate receptor clustering and synaptic function. This work identifies Wg as a novel in vivo glial-secreted factor that specifically modulates assembly of the postsynaptic signaling machinery at the Drosophila NMJ

Pseudovibrio denitrificans strain Z143-1, a heptylprodigiosin-producing bacterium isolated from a Philippine tunicate

Microbial isolate Z143-1 found to be associated with an unidentified tunicate was characterized due to its significant antimicrobial activity. Z143-1 is similar to Pseudovibrio ascidiaceicola and Pseudovibrio denitrificans in morphological, physiological and biochemical characteristics, except for its ability to ferment glucose and produce a characteristic red pigment. Fatty acid methyl ester analysis revealed a predominance of the fatty acid 18:1 ω7c at 80.55%, at levels slightly lower than the Pseudovibrio denitrificans type strain DN34T (87.7%). The mol% G+C of Z143-1 is 54.02, relatively higher than the Pseudovibrio denitrificans type strain DN34T and Pseudovibrio ascidiaceicola with mol% G+C of 51.7 and 51.4, respectively. However, phylogenetic analysis of the 16S rRNA gene sequence of Z143-1 showed 100% similarity with the Pseudovibrio denitrificans type strain DN34T. In this study, the bacterium Z143-1 is reported as a new strain of Pseudovibrio denitrificans. While there is no report of a secondary metabolite for Pseudovibrio denitrificans, Z143-1 produces the red pigment heptylprodigiosin, also known as 16-methyl-15-heptyl-prodiginine, which shows anti-Staphylococcus aureus activity

Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells.</p> <p>Methods</p> <p>HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed.</p> <p>Results</p> <p>5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21^Cip1and p27^Kip1and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU.</p> <p>Conclusion</p> <p>Our findings suggest that the combination therapy with CQ should be a novel therapeutic modality to improve efficacy of 5-FU-based chemotherapy, possibly by inhibiting autophagy-dependent resistance to chemotherapy.</p