Investigation of Chemopreventive and Antiproliferative Potential of Dicliptera roxburghiana.

CONTEXT: Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. OBJECTIVES: Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana. MATERIAL AND METHODS: Crude extract and derived fractions were inspected for their inhibitory potential against nuclear factor KB (NFκB), nitric oxide synthase inhibition, aromatase inhibition and induction of quinone reductase 1 (QR 1). Antiproliferative activity was determined by using various cancer cell lines for example hormone responsive breast cancer cell line MCF-7, estrogen receptor negative breast cancer cell line MDA-MB-231, murine hepatoma cells Hepa 1c1c7, human neuroblastoma cells SK-N-SH and neuroblastoma cells MYCN-2. RESULTS: Ethyl acetate and n-butanol fractions of D. roxburghiana were strongly active against NFκB with IC50 of 16.6 ± 1.3 and 8.4 ± 0.7 µg/ml respectively with 100% survival. Chloroform fraction of the plant exhibited an induction ratio of 2.4 ± 0.09 with CD value of 17.7 µg/ml. Regarding the nitrite assay, the n-hexane fraction exhibited significant inhibition of NO activity with IC50 of 17.8 ± 1.25 µg/ml. The n-butanol fraction exhibited strong antiproliferative activity against IcIc-7 cell lines with IC50 values of 13.6 ± 1.91 µg/ml; against MYCN-2 a cytotoxic effect developed with dose dependence, with IC50 of 12.6 ± 1.24 µg/ml. In antiproliferative activity against SK-N-SH cell lines, chloroform, ethyl acetate and n-butanol fractions were efficiently active with IC50 values of 11.2 ± 0.84, 14.6 ± 1.71 and 16.3 ± 1.57 respectively. DISCUSSION AND CONCLUSION: It was demonstrated that various fractions of D. roxburghiana displayed appreciable anticancer characteristics and could be a potent source for the development of anticancer leads.

Two new monofunctional platinum(II) dithiocarbamate complexes: phenanthriplatin-type axial protection, equatorial-axial conformational isomerism, and anticancer and DNA binding studies.

The syntheses of two platinum(ii) dithiocarbamate complexes (1 and 2) that show quinoplatin- and phenanthriplatin-type axial protection of the Pt-plane are described. The Pt-plane of complex 2 is axially more protected than that of complex 1. Furthermore, both complexes adopt two different stereochemical conformations in the solid state (based on single-crystal X-ray structures) owing to the structurally flexible piperazine backbone; i.e., C-e,e-Anti (1) and C-e,a-Syn (2), where "C" stands for the chair configuration, "e" and "a" stand for the equatorial and axial positions and "Anti" (opposite side) and "Syn" (same side) represent the relative orientations in space of the terminal substituents on the piperazine ring. In complex 2, the C-e,a-Syn conformation may provide additional steric hindrance to the Pt-plane. Despite the lower lipophilicity of 2 as compared to that of 1, the in vitro anticancer action against selected cancer cell lines is better for the former revealing the superior role of the axial protection over lipophilicity in modulating anticancer activity. The activity against the cancer promoting protein NF-κB signifies that the mode of cancer cell death may be the result of hindering the activity of NF-κB in the initiation of apoptosis. The apoptotic mode of cell death has been established earlier in a study using Annexin V-FITC. Finally, DNA binding studies revealed that the complex-DNA adduct formation is spontaneous and the mode of interaction is non-intercalative (electrostatic/covalent).

NF-κB Inhibitory and Antibacterial Helvolic and Fumagillin Derivatives from Aspergillus terreus.

Two new helvolic acid analogues (1 and 2) and one new fumagillin derivative containing an octahydroisobenzofuran moiety (3), together with four known compounds (4-7), were isolated from an Aspergillus terreus, isolated from soil collected from Mauna Kea, the highest mountain in Hawaii. Compound 4 was recorded in SciFinder with a CAS Registry Number of 1379525-35-5, but it was not documented in the cited reference (ACS Chem. Biol. 2012, 7, 137). The structures of compounds 1-4 were elucidated by NMR spectroscopy and HRMS and ECD analysis. Compounds 5 and 6 showed significant inhibitory activity against NF-κB with IC50 values of 2.7 ± 2.6 and 6.5 ± 0.8 µM, respectively. Compounds 1 and 2 were active against S. aureus with MICs of 6.25 and 6.25 µg/mL, respectively, while compound 5 inhibited E. coli with an MIC of 3.12 µg/mL.

Wound healing activity of terpinolene and α-phellandrene by attenuating inflammation and oxidative stress in vitro.

This study was undertaken to investigate the in vitro wound healing effects and the anti-inflammatory and antioxidant activities of terpinolene and α-phellandrene. The in vitro stimulatory effects on the proliferation and migration of fibroblasts were assessed using the scratch assay. The anti-inflammatory activity was evaluated using cell-based assays by investigating their influence on nitric oxide (NO), superoxide anion (O2•-), tumour necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) production and using the TNF-α-induced nuclear factor kappa (NF-κB) assay. Antioxidant activity was determined by the ABTS cation radical scavenging capacity, ferric reducing/antioxidant potential (FRAP), and NO free radical scavenging assays. Terpinolene and α-phellandrene significantly increased the migration and proliferation of fibroblasts and suppressed the pro-inflammatory cytokines IL-6 and TNF-α in a dose-dependent manner. Terpinolene and α-phellandrene at a concentration of 100 µM significantly inhibited NO production (41.3 and 63.8%, respectively) in a macrophage cell-culture-based assay, and resulted in reductions in O2•- production of 82.1 ±â€¯3.5% and 70.6 ±â€¯4.3%, respectively. Moreover, these monoterpenes were verified to suppress NF-κB activity. In summary, terpinolene and α-phellandrene may contribute to broadening clinical options in the treatment of wounds by attenuating inflammation and oxidative stress in vitro.

Phytochemical profile of genotypes of Euterpe edulis Martius - Juçara palm fruits.

Juçara fruit (Euterpe edulis) has received attention due to its similarities to Euterpe oleracea (Açaí). The aim of this study was to evaluate the cytotoxicity, bioactive compounds, antioxidant capacities and chemopreventive activities of the fruit pulps of six populations of E. edulis (J1-J6) and one population of E. espiritosantense from different ecological regions. ESI(-)-FT-ICR-MS was used to evaluate the pulp composition. The varieties J1 and J4 presented higher polyphenol contents, while J2 and J5 showed higher anthocyanin contents. ESI-FT-ICR MS identified cyanidin-3-rutinoside (J1, J2, J3, J4, J5, J7), protocatechuic acid, methylhydroxybenzoate hexoside and rutin (J1 to J7) and malvidin-glicoside (J2 to J5). The J2, J3, J4, J5 and J6 samples inhibited inducible nitric oxide synthase (iNOS). The chemoprevention biomarker quinone reductase was significantly induced by J6. Pulp from plants J3, J4, J6 and J7 significantly reduced the inflammatory cytokine TNF-α, and J6 was selected as having the most potential for cultivation and consumption.

In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway.

BACKGROUND AND AIMS: Terpenes are considered the main components of essential oils and an important source for the identification of novel lead molecules. This study aimed to investigate the in vitro anti-inflammatory activity of L-carveol, L-carvone, and m-cimene (monoterpenes) and of valencene and guaiene (sesquiterpenes). METHODS: The influence on intracellular nitric oxide (NO) and pro- and anti-inflammatory cytokine (TNF-α, IL-1α and IL-10) production and on nuclear factor kappa B (NF-κB) activity was determined using Griess reagent, immunoenzymatic assay kits (ELISA) and chemiluminescence measurements in cell-based assays, respectively. Antioxidant activity was assayed through the protective effect against cellular oxidative damage produced by superoxide anion production (O 2 ·- ) and hydrogen peroxide on macrophages and by the quenching activity of the NO radical. RESULTS AND DISCUSSION: Terpenes reduced the pro-inflammatory cytokines TNF-α and IL-1α and increased the production of IL-10. In addition, the terpenes, especially guaiene (53.3 ± 2.4%) and m-cymene (38.1 ± 0.6%), significantly inhibited NO production in a macrophage cell culture-based assay, whereas no effect was observed in the scavenging activity of this radical. L-carveol and m-cymene significantly inhibited O 2 ·- production with reductions of approximately 68.6 ± 2.2% and 48.2 ± 4.2%, respectively, at a concentration of 10 µM. Moreover, these terpenes were verified to suppress NF-κB activity. The results indicate that these terpenes have therapeutic potential and may be used to suppress inflammatory diseases or as a leading compounds.

Synthesis and Structure-Activity Relationships of Tetrahydro-ß-carboline Derivatives as Anticancer and Cancer-chemopreventive Agents.

BACKGROUND/AIM: There is an unmet clinical need to develop new anticancer and chemopreventive agents. The aim of the present study was to identify ß-carboline derivatives with cancer chemopreventive and therapeutic potential. MATERIALS AND METHODS: Forty-eight tetrahydro-ß-carboline derivatives were synthesized and evaluated for their anticancer and chemopreventive activities, through induction of quinone reductase 1 (QR1), aromatase inhibition, as well as inhibition of nitric oxide (NO) production. RESULTS: 2-((1-Bromonaphthalen-2-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole demonstrated the most potent activity in the QR1 induction assay with an induction ratio value of 3.2 (CD=1.3 µM). The R-isomer of the amide derivative (2-((1-bromonaphthalen-2-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-yl)(4-methylpiperazin-1-yl)methanone was the most potent inhibitor of NO production with a 50% inhibitory concentration, IC50=6.54 µM and had a low cytotoxic effect (IC50=17.98 µM) on RAW 264.7 cells. Subsequent computational docking study revealed that this compound binds to the active site of inducible nitric oxide synthase with favorable interactions. CONCLUSION: our results provided promising ß-carboline leads for further optimization and development with therapeutic potential as new chemopreventive and chemotherapy agents.

Induction of NAD (P)H: Quinone reductase 1 (QR1) and antioxidant activities in vitro of 'Toranja Burarama' (Citrus maxima [Burm.] Merr.).

Toranja 'Burarama', Citrus maxima (Burm.) Merr. (Citrus grandis), is a new citrus discovered in the State of Espírito Santo, Brazil. As several varieties of citrus are known to possess antioxidant and cancer chemopreventive properties, the aim of the study was to evaluate in vitro if this Toranja possess these properties. The antioxidant activity, the potential to induce quinone reductase 1, and the influence on cell viability were measured. ESI(-)FT-ICR MS analysis was also performed and identified flavonoids, coumarins, and fatty acids in the extract. The ethyl acetate and methanolic extracts of the peels presented the highest antioxidant activity in vitro by DPPH (IC50  = 298.3 ± 2.6 µg/ml and 303.8 ± 0.4 µg/ml), ABTS assay (IC50  = 298.2 ± 6.4 µg/ml and 296.4 ± 2.5 µg/ml), and FRAP (IC50  = 234.6 ± 1.8 µg/ml and 398.1 ± 3.8 µg/ml). The ethyl acetate extract of the peel induced quinone reductase 1 activity in Hepa1c1c7 cells, indicating that C. maxima exhibited cancer chemopreventive properties.

Structure-activity relationships and docking studies of synthetic 2-arylindole derivatives determined with aromatase and quinone reductase 1.

In our ongoing effort of discovering anticancer and chemopreventive agents, a series of 2-arylindole derivatives were synthesized and evaluated toward aromatase and quinone reductase 1 (QR1). Biological evaluation revealed that several compounds (e.g., 2d, IC50 = 1.61 µM; 21, IC50 = 3.05 µM; and 27, IC50 = 3.34 µM) showed aromatase inhibitory activity with half maximal inhibitory concentration (IC50) values in the low micromolar concentrations. With regard to the QR1 induction activity, 11 exhibited the highest QR1 induction ratio (IR) with a low concentration to double activity (CD) value (IR = 8.34, CD = 2.75 µM), while 7 showed the most potent CD value of 1.12 µM. A dual acting compound 24 showed aromatase inhibition (IC50 = 9.00 µM) as well as QR1 induction (CD = 5.76 µM) activities. Computational docking studies using CDOCKER (Discovery Studio 3.5) provided insight in regard to the potential binding modes of 2-arylindoles within the aromatase active site. Predominantly, the 2-arylindoles preferred binding with the 2-aryl group toward a small hydrophobic pocket within the active site. The C-5 electron withdrawing group on indole was predicted to have an important role and formed a hydrogen bond with Ser478 (OH). Alternatively, meta-pyridyl analogs may orient with the pyridyl 3'-nitrogen coordinating with the heme group.

Heliotropiumides A and B, new phenolamides with N-carbamoyl putrescine moiety from Heliotropium foertherianum collected in Hawaii and their biological activities.

Two new compounds heliotropiumides A (1) and B (2), phenolamides each with an uncommon carbamoyl putrescine moiety, were isolated from the seeds of a naturalized Hawaiian higher plant, Heliotropium foertherianum Diane & Hilger in the borage family, which is widely used for the treatment of ciguatera fish poisoning. The structures of compounds 1 and 2 were characterized based on MS spectroscopic and NMR analysis, and DP4+ calculations. The absolute configuration (AC) of compound 1 was determined by comparison of its optical rotation with those reported in literature. Compound 2 showed inhibition against NF-κB with an IC50 value of 36µM.

NF-κB inhibitors, unique γ-pyranol-γ-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462.

LC-UV/MS-based metabolomic analysis of the Hawaiian endophytic fungus Paraphaeosphaeria neglecta FT462 led to the identification of four unique mercaptolactated γ-pyranol-γ-lactams, paraphaeosphaerides E-H (1-4) together with one γ-lactone (5) and the methyl ester of compound 2 (11). The structures of the new compounds (1-5 and 11) were elucidated through the analysis of HRMS and NMR spectroscopic data. The absolute configuration was determined by chemical reactions with sodium borohydride, hydrogen peroxide, α-methoxy-α-(trifluoromethyl)phenylacetyl chlorides (Mosher reagents), and DP4 + NMR calculations. All the compounds were tested against STAT3, A2780 and A2780cisR cancer cell lines, E. coli JW2496, and NF-κB. Compounds 1 and 3 strongly inhibited NF-κB with IC50 values of 7.1 and 1.5 µM, respectively.

Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis.

CONTEXT: Sambucus australis Cham. & Schltdl. (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. OBJECTIVE: To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. MATERIALS AND METHODS: The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1-100 µg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. Chemical composition was assessed by LC-MS/MS. RESULTS: Antioxidant activities in the DPPH (IC50 43.5 and 66.2 µg/mL), FRAP (IC50 312.6 and 568.3 µg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 µg/mL) were observed in the leaf and bark ethanol extracts, respectively. Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 µg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 µg/mL, respectively. The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 µg/mL) and Klebsiella pneumoniae (MIC 250 µg/mL). LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. DISCUSSION AND CONCLUSION: The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects.

Brown seaweed Padina gymnospora is a prominent natural wound-care product

ABSTRACT Seaweeds are related to anti-inflammatory, anti-bacterial and anti-noceptive effects. This work aimed to verify the potential of seaweed Padina gymnospora (Kützing) Sonder 1871 to improve wound healing in vitro. P. gymnospora was collected at a bethonic area in Espirito Santo. Methanolic extract of P. gymnospora was obtained by percolation. To determine cytotoxicity, colorimetric MTT tests were performed against normal fibroblasts (L929), macrophages (RAW 264.7) and human ovarian carcinoma (OVCAR-3) cell lines using concentration range of 12–110 µg ml-1. To evaluate in vitro wound healing, monolayer of fibroblasts L929 was seeded and artificial wounded. Cell proliferation was blocked by 5 µg ml-1 Mytomycin C. Nitric oxide inhibition was quantified with Raw 264.7 by Griess reaction. Minimal inhibitory concentration (MIC) against Staphylococcus aureus was determined. Eletrospray ionization with Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS) was applied to detail composition of P. gymnospora methanolic extract. No cytotoxic effect in all cell lines was detected until the maximum concentration of 110 µg ml-1. P. gymnospora promoted significantly migration at the concentration of 25 µg ml-1 (p < 0.05). A prominent inhibition of nitric oxide formation was achieved in a concentration of 20 µg ml-1 of methanolic extract of P. gymnospora (62.06 ± 1.20%). Antibacterial activity against S. aureus could be demonstrated with MIC of 500 µg ml-1. ESI-FT-ICR MS analysis indicated eleven molecules between then, linolenic, oleic and linoleic acid. P. gymnospora favored wound repair in vitro what could be related to its fatty acid composition. In addition, its antimicrobial effect, and NO inhibition activity contribute for a new approach of P. gymnospora as a promise natural product for treatment of cutaneous wound.

Anti-inflammatory triterpenes from the apical bud of Gardenia sootepensis.

Bioassay-guided fractionation of the dichloromethane extract from the apical bud of Gardenia sootepenesis Hutch. (Rubiaceae) led to the isolation of four new cycloartane triterpenes, sootepins F-I (1-4), along with four known derivatives (5-8). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison of the physicochemical data with published values. The isolates were evaluated for cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-α)-induced nuclear factor kappa (NF-κB) activity. Compounds 6-8 inhibited TNF-α-induced NF-κB activity with half maximal inhibitory concentration (IC50) values of 8.3, 5.6, and 6.0µM, respectively; compounds 7 and 8 showed significant NO-inhibitory activity with IC50 values of 3.2 and 2.0µM, respectively.

Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity.

Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8µM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6µM.

Evidence supporting the conceptual framework of cancer chemoprevention in canines.

As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-inducible DNA damage was significantly decreased after consumption of the supplement. The expression of 11 of 84 genes related to oxidative stress was altered. Hematological parameters remained in the reference range. The concept of chemoprevention for the explicit benefit of the canine is compelling since dogs are an important part of our culture. Our results establish a proof-of-principle and provide a framework for improving the health and well-being of "man's best friend".

Anti-inflammatory and Quinone Reductase Inducing Compounds from Fermented Noni (Morinda citrifolia) Juice Exudates.

A new fatty acid ester disaccharide, 2-O-(ß-d-glucopyranosyl)-1-O-(2E,4Z,7Z)-deca-2,4,7-trienoyl-ß-d-glucopyranose (1), a new ascorbic acid derivative, 2-caffeoyl-3-ketohexulofuranosonic acid γ-lactone (2), and a new iridoid glycoside, 10-dimethoxyfermiloside (3), were isolated along with 13 known compounds (4-16) from fermented noni fruit juice (Morinda citrifolia). The structures of the new compounds, together with 4 and 5, were determined by 1D and 2D NMR experiments, as well as comparison with published values. Compounds 2 and 7 showed moderate inhibitory activities in a TNF-α-induced NF-κB assay, and compounds 4 and 6 exhibited considerable quinone reductase-1 (QR1) inducing effects.

Endophytic fungi associated with Taxus fuana (West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents.

CONTEXT: Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery. OBJECTIVE: Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity. MATERIALS AND METHODS: Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-α-induced NFκB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells. RESULTS: Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFκB activity (IC50 values ranging between 0.18 and 17 µg/mL) and five inhibited iNOS (IC50 values ranging between 0.32 and 12.9 µg/mL). In the aromatase assay, only two isolates mediated inhibition (IC50 values 12.2 and 10.5 µg/mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5 µg/mL), and five extracts inhibited the growth of MCF-7 cells (IC50 values ranging from 0.56 to 17.5 µg/mL). Six active cultures were derived from woody parts of the plant material. CONCLUSION: The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents.

Chemical profile of mango (Mangifera indica L.) using electrospray ionisation mass spectrometry (ESI-MS).

Mangifera indica L., mango fruit, is consumed as a dietary supplement with purported health benefits; it is widely used in the food industry. Herein, the chemical profile of the Ubá mango at four distinct maturation stages was evaluated during the process of growth and maturity using negative-ion mode electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI(-)FT-ICR MS) and physicochemical characterisation analysis (total titratable acidity (TA), total soluble solids (TSS), TSS/TA ratio, and total polyphenolic content). Primary (organic acids and sugars) and secondary metabolites (polyphenolic compounds) were mostly identified in the third maturation stage, thus indicating the best stage for harvesting and consuming the fruit. In addition, the potential cancer chemoprevention of the secondary metabolites (phenolic extracts obtained from mango samples) was evaluated using the induction of quinone reductase activity, concluding that fruit polyphenols have the potential for cancer chemoprevention.

Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum.

Chemical investigation of an endophytic fungus Chaetomium globosum isolated from leaves of Wikstroemia uva-ursi led to the isolation of two new azaphilones, chaetoviridins J and K (1 and 3), along with five known derivatives (2 and 4-7). The structures of azaphilones were determined by NMR, X-ray diffraction, Mosher's method, and CD analysis. The isolated compounds were evaluated for their cancer chemopreventive-potential based on their abilities to inhibit tumor necrosis factor alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB). Compounds 4, 5, 7, and synthetic 8 and 9 inhibit nitric oxide (NO) production with IC50 values in the range of 0.3-5.8 µM. Compounds 4, 5, and 9 also displayed (TNF-α)-induced NF-κB activity with IC50 values in the range of 0.9-5.1 µM.