Structure-Based Identification of Potent Natural Product Chemotypes as Cannabinoid Receptor 1 Inverse Agonists.

Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands. Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market. This limitation amplifies the need for new agents with reduced or no CNS-mediated side effects. We are interested in the discovery of new natural product chemotypes as CB1 antagonists, which may serve as good starting points for further optimization towards the development of CB1 therapeutics. In search of new chemotypes as CB1 antagonists, we screened the in silico purchasable natural products subset of the ZINC12 database against our reported CB1 receptor model using the structure-based virtual screening (SBVS) approach. A total of 18 out of 192 top-scoring virtual hits, selected based on structural diversity and key protein⁻ligand interactions, were purchased and subjected to in vitro screening in competitive radioligand binding assays. The in vitro screening yielded seven compounds exhibiting >50% displacement at 10 µM concentration, and further binding affinity (Ki and IC50) and functional data revealed compound 16 as a potent and selective CB1 inverse agonist (Ki = 121 nM and EC50 = 128 nM) while three other compounds-2, 12, and 18-were potent but nonselective CB1 ligands with low micromolar binding affinity (Ki). In order to explore the structure⁻activity relationship for compound 16, we further purchased compounds with >80% similarity to compound 16, screened them for CB1 and CB2 activities, and found two potent compounds with sub-micromolar activities. Most importantly, these bioactive compounds represent structurally new natural product chemotypes in the area of cannabinoid research and could be considered for further structural optimization as CB1 ligands.

New antimalarial norterpene cyclic peroxides from Xisha Islands sponge Diacarnus megaspinorhabdosa.

Four new norterpene cyclic peroxides (1-4), together with three known norterpene cyclic peroxides were isolated from the Xisha Islands Sponge Diacarnus megaspinorhabdosa. Their structures were elucidated on the basis of spectroscopic analyses and comparison with the related model compounds. The compounds (1-7) were evaluated for the inhibitory activity against the malaria parasite Plasmodium falciparum, all of them showed significant antimalarial activity with IC50 values in the range of 1.6-8.6 µM.

Adsorption separation of carbon dioxide from flue gas by a molecularly imprinted adsorbent.

CO2 separation by molecularly imprinted adsorbent from coal-fired flue gas after desulfurization system has been studied. The adsorbent was synthesized by molecular imprinted technique, using ethanedioic acid, acrylamide, and ethylene glycol dimethacrylate as the template, functional monomer, and cross-linker, respectively. According to the conditions of coal-fired flue gas, the influencing factors, including adsorption temperature, desorption temperature, gas flow rate, and concentrations of CO2, H2O, O2, SO2, and NO, were studied by fixed bed breakthrough experiments. The experimental conditions were optimized to gain the best adsorption performance and reduce unnecessary energy consumption in future practical use. The optimized adsorption temperature, desorption temperature, concentrations of CO2, and gas flow rate are 60 °C, 80 °C, 13%, and 170 mL/min, respectively, which correspond to conditions of practical flue gases to the most extent. The CO2 adsorption performance was nearly unaffected by H2O, O2, and NO in the flue gas, and was promoted by SO2 within the emission limit stipulated in the Chinese emission standards of air pollutants for a thermal power plant. The maximum CO2 adsorption capacity, 0.57 mmol/g, was obtained under the optimized experimental conditions, and the SO2 concentration was 150 mg/m(3). The influence mechanisms of H2O, O2, SO2, and NO on CO2 adsorption capacity were investigated by infrared spectroscopic analysis.

Cytotoxic aaptamine derivatives from the South China Sea sponge Aaptos aaptos.

Nine new aaptamine derivatives (1-9), together with three known related compounds (10-12), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated on the basis of spectroscopic analyses. Structurally, compound 1 possesses a piperidinyl group fused to a demethyl(oxy)aaptamine moiety, whereas compounds 3-6 share an imidazole-fused 1H-benzo[de][1,6]naphthyridin-2(4H)-one skeleton. The cytotoxic activities of the compounds were evaluated against various human cancer cell lines, and compounds 2, 8, 11, and 12 showed potent cytotoxicities against HL60, K562, MCF-7, KB, HepG2, and HT-29 cells, with IC50 values in the range of 0.03 to 8.5 µM.

Antileukemic α-pyrone derivatives from the endophytic fungus Alternaria phragmospora.

Four new (1-4) and two known (5 and 6) α-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl-5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran-2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6). Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with IC50 values of 2.2 and 0.9 µM and against K562 cells with IC50 values of 4.5 and 1.5 µM, respectively.

Liver X receptor and peroxisome proliferator-activated receptor agonist from Cornus alternifolia.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptors superfamily and are transcription factors activated by specific ligands. Liver X receptors (LXR) belong to the nuclear hormone receptors and have been shown to play an important role in cholesterol homeostasis. From the previous screening of several medicinal plants for potential partial PPARγ agonists, the extracts of Cornus alternifolia were found to exhibit promising bioactivity. In this paper, we report the isolation and structural elucidation of four new compounds and their potential as ligands for PPAR. METHODS: The new compounds were extracted from the leaves of C. alternifolia and fractionated by high-performance liquid chromatography. Their structures were elucidated on the basis of spectroscopic evidence and analysis of their hydrolysis products. RESULTS: Three new iridoid glycosides including an iridolactone, alternosides A-C (1-3), a new megastigmane glycoside, cornalternoside (4) and 10 known compounds, were obtained from the leaves of C. alternifolia. Kaempferol-3-O-ß-glucopyranoside (5) exhibited potent agonistic activities for PPARα, PPARγ and LXR with EC50 values of 0.62, 3.0 and 1.8 µM, respectively. CONCLUSIONS: We isolated four new and ten known compounds from C. alternifolia, and one known compound showed agonistic activities for PPARα, PPARγ and LXR. GENERAL SIGNIFICANCE: Compound 1 is the first example of a naturally occurring iridoid glycoside containing a ß-glucopyranoside moiety at C-6.

Systematic study of 1,2,3-triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases.

A series of thirty 1,2,3-triazolylsterols, inspired by azasterols with proven antiparasitic activity, were prepared by a stereocontrolled synthesis. Ten of these compounds constitute chimeras/hybrids of 22,26-azasterol (AZA) and 1,2,3-triazolyl azasterols. The entire library was assayed against the kinetoplastid parasites Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, the causatives agents for visceral leishmaniasis, Chagas disease, and sleeping sickness, respectively. Most of the compounds were active at submicromolar/nanomolar concentrations with high selectivity index, when compared to their cytotoxicity against mammalian cells. Analysis of in silico physicochemical properties were conducted to rationalize the activities against the neglected tropical disease pathogens. The analogs with selective activity against L. donovani (E4, IC50 0.78 µM), T brucei (E1, IC50 0.12 µM) and T. cruzi (B1- IC50 0.33 µM), and the analogs with broad-spectrum antiparasitic activities against the three kinetoplastid parasites (B1 and B3), may be promising leads for further development as selective or broad-spectrum antiparasitic drugs.

Effect of Raspberry Ketone on Normal, Obese and Health-Compromised Obese Mice: A Preliminary Study.

Raspberry ketone (RK)-an aromatic compound found mostly in red raspberries (Rubus idaeus) is widely used as an over the counter product for weight loss. The present study was conducted to determine adverse effects associated with RK in obese and health-compromised obese mice. Two sets of experiments were conducted on normal obese and health-compromised obese mice treated with RK for a duration of 10 days. Obese conditions were induced by feeding mice a high fat diet for 10 weeks, while the health compromised obese mouse model was developed by a single intraperitoneal injection of a nontoxic dose of lipopolysaccharide (LPS) (6 mg/kg) to obese mice. Results showed that RK (165, 330, and 500 mg/kg) under obese as well as health-compromised condition retarded the gain in body weights as compared to the control groups. RK at doses 330 and 500 mg/kg resulted in 67.6 and 50% mortality, respectively in normal obese mice and 70% mortality was observed in health-compromised obese mice treated with RK at 500 mg/kg. At higher doses deaths were observed earlier than those given lower doses of RK. Significant elevations in blood alanine transaminase (ALT) were also observed with RK treatment in obese mice. Blood glucose levels were significantly elevated in all groups of mice treated with RK. This study suggests that higher doses of RK may cause adverse effects in health compromised conditions. Under these conditions, prolonged use of RK, especially in high doses, may pose a health hazard.

Transcriptome analysis of the toxic mechanism of nanoplastics on growth, photosynthesis and oxidative stress of microalga Chlorella pyrenoidosa during chronic exposure.

The toxicity of nanoplastics to aquatic organisms has been widely studied in terms of biochemical indicators. However, there is little discussion about the underlying toxic mechanism of nanoplastics on microalgae. Therefore, the chronic effect of polystyrene (PS) nanoplastics (80 nm) on Chlorella pyrenoidosa was investigated, in terms of responses at the biochemical and molecular/omic level. It was surprising that both inhibitory and promoting effects of nanoplastcis on C. pyrenoidosa were found during chronic exposure. Before 13 days, the maximum growth inhibition rate was 7.55% during 10 mg/L PS nanoplastics treatment at 9 d. However, the inhibitory effect gradually weakened with the prolongation of exposure time. Interestingly, algal growth was promoted for 1-5 mg/L nanoplastics during 15-21 d exposure. Transcriptomic analysis explained that the inhibitory effect of nanoplastics could be attributed to suppressed gene expression of aminoacyl-tRNA synthetase that resulted in the reduced synthesis of related enzymes. The promotion phenomenon may be due to that C. pyrenoidosa defended against nanoplastics stress by promoting cell proliferation, regulating intracellular osmotic pressure, and accelerating the degradation of damaged proteins and organs. This study is conducive to provide theoretical basis for evaluating the actual hazard of nanoplastics to aquatic organisms.

Epidemiological Characteristics of Influenza A and B in Macau, 2010-2018.

Influenza is one of the major respiratory diseases in humans. Macau is a tourist city with high density of population and special population mobility. The study on the epidemiological characteristics of influenza in Macau should bring great value for preventing influenza in tourist cities like Macau in the world. In this study, we collected a total of 104,874 samples with influenza-like illness (ILI) in Macau from 2010 to 2018. Chi-square test and binary multivariable logistic regression were used to investigate the epidemiological characteristics of influenza A and B in Macau. Among these ILI samples, the overall positive rate is 17.17% for influenza A and 6.97% for influenza B. The epidemics of influenza in three years (i.e., 2012, 2017 and 2018) differ from the remaining years (i.e., normal years). In a normal year, influenza A occurs year-round whereas influenza B is seasonal. Our research shows significant differences in influenza infections between different age groups in normal years. Interestingly, our analysis shows no significant difference between locals and tourists in influenza A and B infection in a normal year, whereas the odds of influenza A in tourists were significantly higher than those in locals in July 2017 and the odds of influenza B in tourists were significantly higher than those in locals in January-February 2012 and January-February 2018. This is possibly attributed by the policy of free vaccination to everyone in Macau. These findings should be valuable for preventing influenza in not only Macau but also the world.

Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management.

BACKGROUND: Medicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach. METHODS: A systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder. RESULTS: Current literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in Dendrobium genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of Dendrobium provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. Dendrobium polysaccharides protect pancreatic ß-cell dysfunction and insulin resistance in liver. Dendrobium polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies. CONCLUSION: Polysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic ß-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.

Effects of synephrine and beta-phenethylamine on human alpha-adrenoceptor subtypes.

Synephrine and beta-phenethylamine, two naturally occurring compounds, are structurally related to ephedrine. In this study, the effects of synephrine and beta-phenethylamine on alpha-adrenergic receptor (alpha-AR) subtypes are investigated in human embryonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-norephedrine. The rank order of binding affinities was found to be the same for the subtypes tested (alpha(1A)-, alpha(2A)-, and alpha(2C)-AR) viz, 1R,2S-norephedrine > beta-phenethylamine > synephrine. Functional studies on the alpha(1A)-AR subtype showed that synephrine was a partial agonist giving a maximal response at 100 microM that was equal to 55.3 % of the L-phenylephrine maximum. In contrast, neither 1R,2S-norephedrine nor beta-phenethylamine exhibited agonist activity at the highest concentration tested (300 microM). beta-Phenethylamine was more potent as an antagonist than 1R,2S-norephedrine and synephrine on the alpha(1A)-AR subtype. Functional studies on the alpha(2A)- and alpha(2C)-AR subtypes indicated that synephrine and beta-phenethylamine did not act as agonists. Similar to 1R,2S-norephedrine, both of these analogs reversed the effect of medetomidine against forskolin-induced cAMP elevations at 300 microM, and the rank order of antagonist potency was: 1R,2S-norephedrine = beta-phenethylamine > synephrine; and beta-phenethylamine > 1R,2S-norephedrine > synephrine, respectively. These differences suggest that the presence of a 4-hydroxy group, as in synephrine, reduced the potency in these subtypes. In conclusion, at the alpha(1A)-AR, synephrine acted as a partial agonist, while beta-phenethylamine did not exhibit any direct agonist activity. Both, synephrine and beta-phenethylamine, may act as antagonists of pre-synaptic alpha(2A/2C)-ARs present in nerve terminals.

Design, synthesis, biological evaluation and docking studies of pterostilbene analogs inside PPARalpha.

Pterostilbene, a naturally occurring analog of resveratrol, has previously shown PPARalpha activation in H4IIEC3 cells and was found to decrease cholesterol levels in animals. In this study, analogs of pterostilbene were synthesized and their ability to activate PPARalpha was investigated. Among analogs that was synthesized (E)-4-(3,5-dimethoxystyryl)phenyl dihydrogen phosphate showed activity higher than pterostilbene and control drug ciprofibrate. Docking of the stilbenes inside PPARalpha showed the presence of important hydrogen bond interactions for PPARalpha activation.

Inhibition of NF-kappaB-mediated transcription and induction of apoptosis by melampolides and repandolides.

PURPOSE: Nuclear factor-kappaB (NF-kappaB) plays a crucial role in the regulation of inflammatory processes, cell proliferation, and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in cancer and inflammation therapy. The aim of this study was to investigate the effects of sesquiterpenes isolated from Asteraceae, namely melampolides (enhydrin, tetraludin A) and repandolides (repandins A, B, D and E) on the activation of NF-kappaB, cell growth of cancer cells, cell cycle progression and apoptosis. In addition, their effects on the activity of cyclooxygenase-2 (COX-2) enzyme were also evaluated. METHODS: Cell-based reporter gene assay was conducted in SW1353 cells. COX-2 enzyme activity and cell growth inhibition was determined by enzyme immunoassay and MTT assay respectively. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assay. RESULTS: In SW1353 cells, transcription mediated by NF-kappaB was inhibited by enhydrin, tetraludin A and repandins A, B, D and E, while Sp-1 mediated transcription was not affected. COX-2 enzyme activity was inhibited by enhydrin, repandin A and E, but not by tetraludin A, repandin B and D. These compounds were effective in inhibiting the growth of a panel of human tumor cell lines in a concentration-dependent manner. Cell cycle analysis and DAPI staining indicated cell cycle arrest in G(2)/M phase and induction of apoptosis. CONCLUSIONS: Enhydrin, tetraludin A and repandins A, B, D and E inhibited tumor cell growth and induced cell cycle arrest and apoptosis. These effects may be related to inhibition of NF-B activation.

Toll-like receptor 2-dependent activation of monocytes by Spirulina polysaccharide and its immune enhancing action in mice.

We reported previously that a high molecular weight polysaccharide fraction (Immulina) from Spirulina was a potent activator of NF-kappa B and induced both IL-1 beta and TNF-alpha mRNAs in THP-1 human monocytes. In the present study, we show that NF-kappa B activation by Immulina is suppressed by antibodies to CD14 and TLR2 but not by antibodies to TLR4. Similarly, NF-kappa B directed luciferase expression was enhanced by Immulina treatment when cells were co-transfected with vectors expressing proteins supporting TLR2- (CD14 and TLR2) but not TLR4-(CD14, TLR4, and MD-2) dependent activation. Mice that consumed a chemically defined chow mixed with an extract containing Immulina exhibited changes in several immune parameters. The ex vivo production of IgA and IL-6 from Peyer's patch cells was enhanced 2-fold and interferon-gamma production from spleen cells was increased 4-fold in Immulina-treated mice. The enhanced production of these factors was most notable with mice that had consumed this extract for 4 or 5 days. These studies shed light on how Immulina activates cells of the innate immune system and suggests that oral consumption of this polysaccharide can enhance components within both the mucosal and systemic immune systems.

Synthesis and in vitro cytotoxic activity of N-, F-, and S-ether derivatives of podophyllotoxin fatty acid adducts.

This paper represents the first synthesis, spectroscopic characterization, and antitumor evaluation of F-, N-, and S-containing C4alpha-FA derivatives of podophyllotoxin. In a synthetic strategy, a FA unit of 4-O-podophyllotoxinyl 12-hydroxyoctadec-Z-9-enoate 2, a derivative of podophyllotoxin, was functionalized at the C-12 position by incorporating the F atom and N-containing moieties. The FA olefin (Z, C-9/C-10) of 2 was hydrogenated to produce a derivative possessing a hydroxy function (C-12) on a saturated C18 FA chain. In another synthetic strategy, two S-ethers of podophyllotoxin (C4alpha) were synthesized from a terminal unsaturated FA analog, 4-O-podophyllotoxinyl undec-10-enoate. Syntheses were achieved through effective synthetic procedures; 1H NMR, 13C NMR, IR, and high-resolution mass data proved excellent tools to characterize these derivatives. In vitro antitumor activity was investigated against a panel of five human neoplastic cell lines, SK-MEL (malignant, melanoma), KB (epidermal carcinoma, oral), BT-549 (ductal carcinoma, breast), SK-OV-3 (ovary carcinoma), and HL-60 (human leukemia). Keeping in view the severe lack of tumor selectivity of podophyllotoxin over normal cells, we assayed new analogs against noncancerous mammalian VERO (African green monkey kidney fibroblast) cell lines to gauge their extent of toxicity. Several of these compounds showed excellent moderation of antitumor activity. In general, we found excellent growth inhibition against the human leukemia cell line (HL-60), particularly for the analogs containing S-ethers and carbamates. None of the compounds were toxic to normal cell lines.

Anticancer activity and possible mode of action of 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate.

4-O-Podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate (PHEFE) is a structurally novel FA analog of podophyllotoxin. In the present study, in vitro effects of PHEFE on a panel of 60 human tumor cell lines and its potential modes of anticancer action were investigated. PHEFE exhibited strong growth-inhibitory action in a number of solid tumor cells in vitro. It did not inhibit tubulin polymerization as podophyllotoxin does; rather, it inhibited the catalytic activity of topoisomerase II. Flow cytometry and staining assay with 4,6-diamidine-2-phenylindole dihydrochloride showed that PHEFE blocked the cell cycle at the G2/M phase and induced apoptosis in HL-60 cells. These analyses suggest that PHEFE has promising anticancer characteristics that differ from podophyllotoxin and etoposide.

Synthesis, spectroscopic, and biological studies of novel estolides derived from anticancer active 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate.

Podophyllotoxin is a well-known natural antitumor agent with severe side effects, which led us to synthesize its numerous analogs in search of product(s) of improved therapeutic potential. Here, we report an efficient method for the synthesis of a series of 4-O-podophyllotoxin estolides with spectral characteristics and their biological studies. The OH of a known molecule, 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate 2, was coupled with the carboxylic groups of different FA with the help of dicyclohexylcarbodiimide and dimethyl aminopyridine (catalyst) to produce high yields of their respective C(4)alpha-estolides 3-11. Spectroscopic techniques, particularly 1H and 13CNMR, proved to be suitable tools to characterize the new compounds. These molecules of greater lipophilic character were tested for their in vitro cytotoxicity against four human solid tumors, one human leukemia cell, and one noncancerobu cell. Compounds 4-6 and 11 showed moderate antileukemic activity; unexpectedly, none were found to be active against solid tumors. Estolides were also investigated for their in vitro activity against tubulin and topoisomerase II proteins. All the compounds showed inhibition of the catalytic activity of topoisomerase II, whereas 6-8 also inhibited tubulin polymerization. These results suggest the need for further screening of these molecules against a larger panel of cancerous cells.

Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin.

Derivatives of podophyllotoxin were prepared by coupling 10 FA with the C4-alpha-hydroxy function of podophyllotoxin. The coupling reactions between FA and podophyllotoxin were carried out by dicyclohexylcarbodiimide in the presence of a catalytic amount of dimethylaminopyridine to produce quantitative yields of desired products. FA incorporated were the following: 10-hydroxydecanoic, 12-hydroxydodecanoic, 15-hydroxypentadecanoic, 16-hydroxyhexadecanoic, 12-hydroxyoctadec-Z-9-enoic, eicosa-Z-5,8,11,14-tetraenoic, eicosa-Z-8,11, 14-trienoic, eicosa-Z-11,14-dienoic, eicosa-Z-11-enoic, and eicosanoic acids. Spectroscopic studies confirmed the formation of the desired products. New molecules were investigated for their in vitro anticancer activity against a panel of human cancer cell lines including SK-MEL, KB, BT-549, SK-OV-3 (solid tumors), and HL-60 (human leukemia) cells. Most of the analogs were cytotoxic against cancerous cells, whereas no effect was observed against normal cells, unlike the parent compound podophyllotoxin, the use of which is limited due to its severe side effects.

Nigrosphaerin A a new isochromene derivative from the endophytic fungus Nigrospora sphaerica.

Nigrosphaerin A, a new isochromene derivative (1), was isolated from the endophytic fungus Nigrospora sphaerica and chemically identified as 3-(3,4-dihydroxyphenyl)-4,6,8-trihydroxy-1H-isochromen-1-one-6-O-ß-d-glucopyranoside. In addition nineteen known compounds (2-20) were isolated from the same fungus and chemically identified. Compounds (1-3, 5, and 7-16) were isolated for the first time from this fungus. In vitro antileukemic, antileishmanial, antifungal, antibacterial and antimalarial activities of (1-20) were examined. Compounds 5, 7, 9 and 10 showed good antileukemic activity against HL60 cells with IC50 values of 0.03, 0.39, 0.2 and 0.4 µg/mL, respectively and against K562 cells with IC50 values of 0.35, 0.35, 0.49 and 0.01 µg/mL, respectively. Compounds 3, 4 and 6 showed moderate antileishmanial activity with IC50 values of 30.2, 26.4 and 36.4 µg/ml, respectively. Compound 7 showed moderate antifungal activity against Cryptococcus neoformans with IC50 value of 14.8 µg/mL.