In vitro cytotoxic activity on KATO-III cancer cell lines of mangiferolic acid purified from Thai Tetragonula laeviceps propolis.

Gastric cancer is a global health concern, but current treatment with chemotherapy and surgery is often inadequate, prompting the exploration of alternative treatments. Propolis is a natural substance collected by bees known for its diverse properties linked to floral sources. The Dichloromethane Partitioned Extract (DPE) from Tetragonula laeviceps propolis, in Bankha district, Thailand was previously shown to possess significant cytotoxicity against KATO-III gastric cancer cells, while showing lower cytotoxicity toward WI-38 normal fibroblast cells. Here, the DPE was further fractionated by column chromatography, identified active fractions, and subjected to structural analysis using nuclear magnetic resonance spectroscopy. Cytotoxicity against KATO-III cells was reevaluated, and programmed cell death was analyzed using flow cytometry. Expression levels of cancer-related genes were measured using quantitative real-time reverse transcriptase PCR. Cardol C15:2 (compound 1) and mangiferolic acid (MF; compound 2) were discovered in the most active fractions following structural analysis. MF exhibited strong cytotoxicity against KATO-III cells (IC50 of 4.78-16.02 µg/mL), although this was less effective than doxorubicin (IC50 of 0.56-1.55 µg/mL). Morphological changes, including decreased cell density and increased debris, were observed in KATO-III cells treated with 30 µg/mL of MF. Significant induction of late-stage apoptosis and necrosis, particularly at 48 and 72 h, suggested potential DNA damage and cell cycle arrest, evidenced by an increased proportion of sub-G1 and S-phase cells. Doxorubicin, the positive control, triggered late apoptosis but caused more necrosis after 72 h. Furthermore, MF at 30 µg/mL significantly increased the expression level of COX2 and NFκB genes linked to inflammation and cell death pathways. This upregulation was consistent at later time points (48 and 72 h) and was accompanied by increased expression of CASP3 and CASP7 genes. These findings suggest MF effectively induces cell death in KATO-III cells through late apoptosis and necrosis, potentially mediated by upregulated inflammation-related genes.

Exploring the Relationships Between Bacterial Community, Taste-Enhancing Peptides and Aroma in Thai Fermented Fish (Pla-ra).

As a traditional Thai condiment, Pla-ra is used to add flavor and richness to dishes. Nine treatment combinations of Pla-ra formulations created from 3 types of fish (Mor fish, Kradee fish, and Mor + Kradee fish) and 4 different carbohydrate sources (none, rice bran, roasted rice, and rice bran─roasted rice mixture) were studied through a 12 month fermentation period (1, 3, 5, 7, 8, 9, 10, 11, and 12 months). 16S rRNA Next Generation Sequencing (NGS) and LC-MS/MS techniques were used to analyze the microbial diversity and identify taste-enhancing peptides. Descriptive sensory analysis was performed on the extracts of the 108 Pla-ra samples mixed in a model broth. Koku perception and saltiness-enhancing attributes were clearly perceived and dominant in all samples, even though glutamyl peptides, including γ-Glu-Val-Gly, were found at subthreshold levels. The samples from mixed fish and Mor fish fermented with roasted ground rice and rice bran for 12 months had the most typical Pla-ra odors and tastes and had high taste-enhancing activities. NGS analysis revealed the presence of bacteria containing a large number of protease and aminopeptidase genes in the samples. Bacillus spp., Gallicola spp., and Proteiniclasticum spp. correlated well with the generation of glutamyl and arginyl peptides and typical odors in the samples. These results confirmed the typical sensory quality of Pla-ra depended on protein sources, carbohydrate sources, and bacteria communities. Further optimization of the microbial composition found could lead to the development of starter cultures to control and promote flavor development in fermented fish products.

Garcowacinols A-J, cytotoxic polyprenylated benzoylphloroglucinol derivatives from the twigs of Garcinia cowa.

Ten undescribed polyprenylated benzoylphloroglucinol derivatives named garcowacinols A‒J (1-10) and four known analogues (11-14) were isolated from the twigs of Garcinia cowa. Their structures were determined by spectroscopic data analysis (1D and 2D NMR and HRESIMS), and their absolute configurations were established based on NOESY and ECD data. All isolated compounds were evaluated for their cytotoxicity against five types of human cancer cells (KB, HeLa S3, MCF-7, Hep G2, and HT-29) as well as Vero cells by MTT colorimetric assay. Garcowacinol C was significantly active against all the five cancer cells with IC50 values in the range of 0.61-9.50 µM. Selective proliferative inhibitions were observed on garcowacinol F and 7-epiclusianone against KB cells, and guttiferone Q toward MCF-7 cells with IC50 values less than 10 µM.

Thioether and Ether Furofuran Lignans: Semisynthesis, Reaction Mechanism, and Inhibitory Effect against α-Glucosidase and Free Radicals.

The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study, the semisynthesis of 28 furofuran lignans using samin (5) as the starting material is described. Our methodology involved the protonation of samin (5) to generate an oxocarbenium ion followed by the attack from two different nucleophiles, namely, thiols (RSH) and alcohols (ROH). The highly diastereoselective thioether and ether furofuran lignans were obtained, and their configurations were confirmed by 2D NMR and X-ray crystallography. The mechanism underlying the reaction was studied by monitoring 1H NMR and computational calculations, that is, the diastereomeric α- and ß-products were equally formed through the SN1-like mechanism, while the ß-product was gradually transformed via an SN2-like mechanism to the α-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against α-glucosidases and free radicals, the lignans 7f and 7o of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the α-glucosidase inhibition of 7f and 7o were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both 7f and 7o possessed promising antidiabetic activity, while simultaneously inhibiting α-glucosidases and free radicals.

Developmental effects of sesamolin on zebrafish (Danio rerio) embryos.

Sesamolin is one of the major active compounds found in sesame seeds (Sesamum indicum L.) that are commonly and increasingly used as an ingredient in cuisines and various food products. The compound has been reported to have several pharmaceutical activities such as antioxidant, antimicrobial, neuroprotective, and anticancer. However, the toxicological profile of sesamolin does not currently include developmental toxicity. In this study, we assessed sesamolin toxicity to embryonic development of zebrafish by exposure for 72 h at concentrations ranging from 10 to 50 µM. The evaluation revealed that sesamolin did not affect survival and hatching rates. However, it did induce embryo malformations and reduced embryonic heart rates in a dose-dependent manner. By qRT-PCR analysis, it downregulated the expression of oxidative stress-related genes, including superoxide dismutase 1 (sod1), catalase (cat), and glutathione S-transferase pi 2 (gstp2). Alkaline phosphatase staining of embryos revealed that sesamolin inhibited the development of subintestinal vessels, and hemoglobin staining revealed a negative impact on embryonic erythropoiesis. These findings showed that sesamolin affected genes related to angiogenesis and erythropoiesis. The risks of sesamolin to embryonic development found in this study may imply similar effects in humans and other mammals.

Safflospermidines from the bee pollen of Helianthus annuus L. exhibit a higher in vitro antityrosinase activity than kojic acid.

BACKGROUND: Ozone deterioration in the atmosphere has become a severe problem causing overexposure of ultraviolet light, which results in humans in melanin overproduction and can lead to many diseases, such as skin cancer and melasma, as well as undesirable esthetic appearances, such as freckles and hyperpigmentation. Although many compounds inhibit melanin overproduction, some of them are cytotoxic, unstable, and can cause skin irritation. Thus, searching for new natural compounds with antityrosinase activity and less/no side effects is still required. Here, bee pollen derived from sunflower (Helianthus annuus L.) was evaluated. MATERIALS AND METHODS: Sunflower bee pollen (SBP) was collected from Apis mellifera bees in Lopburi province, Thailand in 2017, extracted by methanol and sequentially partitioned with hexane and dichloromethane (DCM). The in vitro antityrosinase activity was evaluated using mushroom tyrosinase and the half maximal inhibitory concentration (IC50) is reported. The antioxidation activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and reported as the half maximal effective concentration. Two pure compounds with antityrosinase activity were isolated by silica gel 60 column chromatography (SG60CC) and high performance liquid chromatography (HPLC), and their chemical structure deduced by Nuclear Magnetic Resonance (NMR) analysis. RESULTS: The DCM partitioned extract of SBP (DCMSBP) had an antityrosinase activity (IC50, 159.4 µg/mL) and was fractionated by SG60CC, providing five fractions (DCMSBP1-5). The DCMSBP5 fraction was the most active (IC50 = 18.8 µg/mL) and further fractionation by HPLC gave two active fractions, revealed by NMR analysis to be safflospermidine A and B. Interestingly, both safflospermidine A and B had a higher antityrosinase activity (IC50 of 13.8 and 31.8 µM, respectively) than kojic acid (IC50 of 44.0 µM). However, fraction DCMSBP5 had no significant antioxidation activity, while fractions DCMSBP1-4 showed a lower antioxidation activity than ascorbic acid. CONCLUSION: Safflospermidine A and B are potential natural tyrosinase inhibitors.

A novel flavanone derivative inhibits dengue virus fusion and infectivity.

Dengue infection is a global burden affecting millions of world population. Previous studies indicated that flavanones were potential dengue virus inhibitors. We discovered that a novel flavanone derivative, 5-hydroxy-7-methoxy-6-methylflavanone (FN5Y), inhibited DENV2 pH-dependent fusion in cell-based system with strong binding efficiency to DENV envelope protein at K (P83, L107, K128, L198), K' (T48, E49, A50, L198, Q200, L277), X' (Y138, V354, I357), and Y' (V97, R99, N103, K246) by molecular dynamic simulation. FN5Y inhibited DENV2 infectivity with EC50s (and selectivity index) of 15.99 ±â€¯5.38 (>6.25), and 12.31 ±â€¯1.64 (2.23) µM in LLC/MK2 and Vero cell lines, respectively, and inhibited DENV4 at 11.70 ±â€¯6.04 (>8.55) µM. CC50s in LLC/MK2, HEK-293, and HepG2 cell lines at 72 h were higher than 100 µM. Time-of-addition study revealed that the maximal efficacy was achieved at early after infection corresponded with pH-dependent fusion. Inactivating the viral particle, interfering with cellular receptors, inhibiting viral protease, or the virus replication complex were not major targets of this compound. FN5Y could become a potent anti-flaviviral drug and can be structurally modified for higher potency using simulation to DENV envelope as a molecular target.

Molecular mechanism of cardol, isolated from Trigona incisa stingless bee propolis, induced apoptosis in the SW620 human colorectal cancer cell line.

BACKGROUND: Cardol is a major bioactive constituent in the Trigona incisa propolis from Indonesia, with a strong in vitro antiproliferative activity against the SW620 colorectal adenocarcinoma cell line (IC50 of 4.51 ± 0.76 µg/mL). Cardol induced G0/G1 cell cycle arrest and apoptotic cell death. The present study was designed to reveal the mechanism of cardol's antiproliferative effect and induction of apoptosis. METHODS: Changes in cell morphology were observed by light microscopy. To determine whether the mitochondrial apoptotic pathway was involved in cell death, caspase-3 and caspase-9 activities, western blot analysis, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assayed. RESULTS: Changes in the cell morphology and the significantly increased caspase-3 and caspase-9 activities, plus the cleavage of pro-caspase-3, pro-caspase-9 and PARP, supported that cardol caused apoptosis in SW620 cells within 2 h after treatment by cardol. In addition, cardol decreased the mitochondrial membrane potential while increasing the intracellular ROS levels in a time- and dose-dependent manner. Antioxidant treatment supported that the cardol-induced cell death was dependent on ROS production. CONCLUSION: Cardol induced cell death in SW620 cells was mediated by oxidative stress elevation and the mitochondrial apoptotic pathway, and these could be the potential molecular mechanism for the antiproliferative effect of cardol.

Cardanol isolated from Thai Apis mellifera propolis induces cell cycle arrest and apoptosis of BT-474 breast cancer cells via p21 upregulation.

BACKGROUND: Cardanol was previously reported to be an antiproliferative compound purified from Thai Apis mellifera propolis. By morphology, it could induce the cell death to many cancer cell lines but not the control (non-transformed human foreskin fibroblast cell line, Hs27). Here, it was aimed to evaluate the molecular effects of cardanol on breast cancer derived cell line (BT-474). METHODS: Morphological changes in BT-474 cells induced by cardanol compared to doxorubicin were evaluated by light microscopy, cytotoxicity by using the 3- (4, 5-dimethyl-thiazol-2-yl) 2, 5-diphenyl-tetrazolium bromide (MTT) assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidium iodide and annexin-V stained cells, and changes in the expression level of genes involved in the control of apoptosis and the cell cycle by quantitative reverse transcriptase-PCR (qRT-PCR) and western blot analyses. RESULTS: It revealed that cardanol induced a time- and dose-dependent cytotoxicity along with cell shrinkage and detachment from substratum. Cardanol caused cell cycle arrest at the G1 subphase (as opposed to at the G2/M subphase seen with doxorubicin) and cell death by late apoptosis, with both late apoptosis (27.2 ± 1.1 %) and necrosis (25.4 ± 1.4 %) being found in cardanol treated cells after 72 h, compared to a lower proportion of apoptosis (4.3 ± 0.4 %) and higher proportion of necrosis (35.8 ± 13.0 %) induced by doxorubicin. Moreover, cardanol changed the transcript expression levels of genes involved in the control of apoptosis (increased DR5 and Bcl-2 expression and decreased Mcl-1, MADD and c-FLIPP) and cell division (increased p21 and E2FI and decreased cyclin D1, cyclin E, CDK4 and CDK2 expression), as well as increasing the level of p21 p-ERK, p-JNK and p-p38 and decreasing cyclin D. This accounts for the failure to progress from the G1 to the S subphase. CONCLUSION: Cardanol is a potential chemotherapeutic agent for breast cancer.

Propolis from the Stingless Bee Trigona incisa from East Kalimantan, Indonesia, Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines.

BACKGROUND: Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It was established that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 colon cancer cell line (6% cell survival in 20 µg/mL). MATERIALS AND METHODS: Propolis from T. incisa was extracted with methanol and further partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity of the extracts was assessed by the MTT assay against human colon (SW620), liver (Hep-G2), gastric (KATO-III), lung (Chago) and breast (BT474) cancer derived cell lines. The active fractions were further enriched by silica gel quick column, absorption and size exclusion chromatography. The purity of each fraction was checked by thin layer chromatography. Cytotoxicity in BT-474 cells induced by cardanol compared to doxorubicin were evaluated by MTT assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidium iodide and annexin-V stained cells. RESULTS: A cardol isomer was found to be the major compound in one active fraction (F45) of T. incisa propolis, with a cytotoxicity against the SW620 (IC50 of 4.51±0.76 µg/mL), KATO-III (IC50 of 6.06±0.39 µg/mL), Hep-G2 (IC50 of 0.71±0.22 µg/mL), Chago I (IC50 of 0.81±0.18 µg/mL) and BT474 (IC50 of 4.28±0.14 µg/mL) cell lines. Early apoptosis (programmed cell death) of SW620 cells was induced by the cardol containing F45 fraction at the IC50 and IC80 concentrations, respectively, within 2-6 h of incubation. In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. CONCLUSIONS: Indonesian stingless bee (T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardol or 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells in an early period (≤6 h) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer chemotherapy.

Effect of three fatty acids from the leaf extract of Tiliacora triandra on P-glycoprotein function in multidrug-resistant A549RT-eto cell line.

BACKGROUND: Cancer cells have the ability to develop resistance to chemotherapy drugs, which then leads to a reduced effectiveness and success of the treatment. Multidrug resistance (MDR) involves the resistance in the same cell/tissue to a diverse range of drugs of different structures. One of the characteristics of MDR is an overexpression of P-glycoprotein (P-gp), which causes the efflux of the accumulated drug out of the cell. The MDR human non-small cell lung carcinoma cell line with a high P-gp expression level (A549RT-eto) was used to investigate the bioactive compounds capable of reversing the etoposide resistance in this cell line. MATERIALS AND METHODS: The leaves of Tiliacora triandra were sequentially extracted with hexane, dichloromethane, methanol and water. Only the hexane extract reduced the etoposide resistance of the A549RT-eto cell line, and was further fractionated by column chromatography using the TLC-pattern and the restoration of etoposide sensitivity as the selection criteria. RESULTS: The obtained active fraction (F22) was found by nuclear magnetic resonance and gas chromatography-mass spectroscopy analyses to be comprised of a 49.5:19.6:30.9 (w/w/w) mixture of hexadecanoic: octadecanoic acid: (Z)-6-octadecenoic acids. This stoichiometric mixture was recreated using pure fatty acids (MSFA) and gave a similar sensitization to etoposide and enhanced the relative rate of rhodamine-123 accumulation to a similar extent as F22, supporting the action via reducing P-gp activity. In contrast, the fatty acids alone did not show this effect. CONCLUSION: This is the first report of the biological activity from the leaves of T. triandra as a potential source of a novel chemosensitizer.

Feroniellin A-induced autophagy causes apoptosis in multidrug-resistant human A549 lung cancer cells.

During the screening of natural chemicals that can reverse multidrug resistance in human A549 lung cancer cells resistant to etoposide (A549RT-eto), we discovered that Feroniellin A (FERO), a novel furanocoumarin, shows toxicity toward A549RT-eto cells in a dose- and time-dependent manner. FERO reduced the expression of NF-κB, leading to downregulation of P-glycoprotein (P-gp), encoded by MDR1, which eventually sensitized A549RT-eto cells to apoptosis. FERO specifically diminished transcription and promoter activity of MDR1 but did not inhibit the expression of other multidrug resistance genes MRP2 and BCRP. Moreover, co-administration of FERO with Bay11-7802, an inhibitor of NF-κB, accelerated apoptosis of A549RT-eto cells through decreased expression of P-gp, indicating that NF-κB is involved in multidrug resistance. Conversely, addition of Z-VAD, a pan-caspase inhibitor, blocked FERO-induced apoptosis in A549RT-eto cells but did not block downregulation of P-gp, indicating that a decrease in P-gp expression is necessary but not sufficient for FERO-induced apoptosis. Interestingly, we found that FERO also induces autophagy, which is characterized by the conversion of LC3 I to LC3 II, induction of GFP-LC3 puncta, enhanced expression of Beclin-1 and ATG5, and inactivation of mTOR. Furthermore, suppression of Beclin-1 by siRNA reduced FERO-induced apoptosis in A549RT-eto cells and activation of autophagy by rapamycin accelerated FERO-induced apoptosis, suggesting that autophagy plays an active role in FERO-induced apoptosis. Herein, we report that FERO reverses multidrug resistance in A549RT-eto cells and exerts its cytotoxic effect by induction of both autophagy and apoptosis, which suggests that FERO can be a useful anticancer drug for multidrug-resistant lung cancer.

Feroniellides C-E, new apotirucallane triterpenoids from the stem bark of Feroniella lucida.

Bioassay-directed isolation of Feroniella lucida stem bark yielded three new apotirucallane triterpenoids named feroniellides C-E. The structures of the new compounds were established by extensive analysis of spectroscopic data. Of triterpenoids examined, feroniellides D and E revealed anticancer activity against KB and HeLa cells with IC50 values in range of 3.4-14.2 µg mL(-1), which are significantly more potent than feroniellides A-C (IC50 25.5-60.0 µg mL(-1)). The present investigation suggests that an isovalerate moiety in feroniellides D and E is possibly associated with exerting cytotoxicity against cancer cells.

In vitro antiproliferative/cytotoxic activity on cancer cell lines of a cardanol and a cardol enriched from Thai Apis mellifera propolis.

BACKGROUND: Propolis is a complex resinous honeybee product. It is reported to display diverse bioactivities, such as antimicrobial, anti-inflammatory and anti-tumor properties, which are mainly due to phenolic compounds, and especially flavonoids. The diversity of bioactive compounds depends on the geography and climate, since these factors affect the floral diversity. Here, Apis mellifera propolis from Nan province, Thailand, was evaluated for potential anti-cancer activity. METHODS: Propolis was sequentially extracted with methanol, dichloromethane and hexane and the cytotoxic activity of each crude extract was assayed for antiproliferative/cytotoxic activity in vitro against five human cell lines derived from duet carcinoma (BT474), undifferentiated lung (Chaco), liver hepatoblastoma (Hep-G(2)), gastric carcinoma (KATO-III) and colon adenocarcinoma (SW620) cancers. The human foreskin fibroblast cell line (Hs27) was used as a non-transformed control. Those crude extracts that displayed antiproliferative/cytotoxic activity were then further fractionated by column chromatography using TLC-pattern and MTT-cytotoxicity bioassay guided selection of the fractions. The chemical structure of each enriched bioactive compound was analyzed by nuclear magnetic resonance and mass spectroscopy. RESULTS: The crude hexane and dichloromethane extracts of propolis displayed antiproliferative/cytotoxic activities with IC(50) values across the five cancer cell lines ranging from 41.3 to 52.4 µg/ml and from 43.8 to 53.5 µg/ml, respectively. Two main bioactive components were isolated, one cardanol and one cardol, with broadly similar in vitro antiproliferation/cytotoxicity IC(50) values across the five cancer cell lines and the control Hs27 cell line, ranging from 10.8 to 29.3 µg/ml for the cardanol and < 3.13 to 5.97 µg/ml (6.82 - 13.0 µM) for the cardol. Moreover, both compounds induced cytotoxicity and cell death without DNA fragmentation in the cancer cells, but only an antiproliferation response in the control Hs27 cells However, these two compounds did not account for the net antiproliferation/cytotoxic activity of the crude extracts suggesting the existence of other potent compounds or synergistic interactions in the propolis extracts. CONCLUSION: This is the first report that Thai A. mellifera propolis contains at least two potentially new compounds (a cardanol and a cardol) with potential anti-cancer bioactivity. Both could be alternative antiproliferative agents for future development as anti-cancer drugs.

In vitro antiproliferative activity of partially purified Trigona laeviceps propolis from Thailand on human cancer cell lines.

BACKGROUND: Cancers are some of the leading causes of human deaths worldwide and their relative importance continues to increase. Since an increasing proportion of cancer patients are acquiring resistance to traditional chemotherapeutic agents, it is necessary to search for new compounds that provide suitable specific antiproliferative affects that can be developed as anticancer agents. Propolis from the stingless bee, Trigona laeviceps, is one potential interesting source that is widely available and cultivatable (as bee hives) in Thailand. METHODS: Propolis (90 g) was initially extracted by 95% (v/v) ethanol and then solvent partitioned by sequential extractions of the crude ethanolic extract with 40% (v/v) MeOH, CH2Cl2 and hexane. After solvent removal by evaporation, each extract was solvated in DMSO and assayed for antiproliferative activity against five cancer (Chago, KATO-III, SW620, BT474 and Hep-G2) and two normal (HS27 fibroblast and CH-liver) cell lines using the MTT assay. The cell viability (%) and IC50 values were calculated. RESULTS: The hexane extract provided the highest in vitro antiproliferative activity against the five tested cancer cell lines and the lowest cytotoxicity against the two normal cell lines. Further fractionation of the hexane fraction by quick column chromatography using eight solvents of increasing polarity for elution revealed the two fractions eluted with 30% and 100% (v/v) CH2Cl2 in hexane (30DCM and 100DCM, respectively) had a higher anti-proliferative activity. Further fractionation by size exclusion chromatography lead to four fractions for each of 30DCM and 100DCM, with the highest antiproliferative activity on cancer but not normal cell lines being observed in fraction# 3 of 30DCM (IC50 value of 4.09 - 14.7 µg/ml). CONCLUSIONS: T. laeviceps propolis was found to contain compound(s) with antiproliferative activity in vitro on cancer but not normal cell lines in tissue culture. The more enriched propolis fractions typically revealed a higher antiproliferative activity (lower IC50 value). Overall, propolis from Thailand may have the potential to serve as a template for future anticancer-drug development.

New antitumour fungal metabolites from Alternaria porri.

Chemical investigation of the onion pathogenic fungus Alternaria porri resulted in the isolation of two new phthalides named zinnimide (2) and deprenylzinnimide (8), along with a new bianthraquinone, alterporriol F (10). The structures of the new metabolites were characterised by spectroscopic analysis and chemical degradation. Of the new compounds isolated, alterporriol F was highly cytotoxic towards HeLa and KB cells, with IC(50) values of 6.5 and 7.0 microg mL(-1).

9-epi-Viridiol, a novel cytotoxic furanosteroid from soil fungus Trichoderma virens.

A novel furanosteroid named 9-epi-viridiol (1), along with viridiol (2) and mevalonic acid (3), was isolated from Trichoderma virens. The structure of 1 was verified by combined spectroscopic data (COSY, HSQC, HMBC and NOESY) to be a C-9 epimer of viridiol. 9-epi-Viridiol exhibited cytotoxicity towards HeLa and KB cells with IC50 values of 19 and 50 microg mL(-1), respectively.

Mycapolyols A-F, new cytotoxic metabolites of mixed biogenesis from the marine sponge Mycale izuensis.

[structure: see text]. Mycapolyols A-F (1-6), six new unusual PKS/NRPS metabolites, were isolated from the marine sponge Mycale izuensis. The gross structures were elucidated by analysis of spectroscopic data, while the stereochemistry was established using chemical method and the universal NMR database.

Mycaperoxide H, a new cytotoxic norsesterterpene peroxide from a Thai marine sponge Mycale sp.

Mycaperoxide H, a new cyclic norsesterterpene peroxide, was isolated from a Thai marine sponge Mycalesp. The structure of mycaperoxide H was deduced by spectroscopic and chemical analysis. Mycaperoxide H was cytotoxic against HeLa cells with an IC(50) value of 0.8 microgram/mL.

Isolation of a new mycalolide from the marine sponge Mycale izuensis.

Bioassay-directed fractionation of the lipophilic extract of the marine sponge Mycale izuensis led to the isolation of cytotoxic mycalolides including a new compound, 30,32-dihydroxymycalolide A (1). Its structure including absolute stereochemistry was deduced by spectroscopic and chemical methods. Compound 1 was cytotoxic against HeLa cells with an IC(50) value of 2.6 ng/mL.