Ligiamycins A and B, Decalin-Amino-Maleimides from the Co-Culture of Streptomyces sp. and Achromobacter sp. Isolated from the Marine Wharf Roach, Ligia exotica.

Streptomyces sp. GET02.ST and Achromobacter sp. GET02.AC were isolated together from the gut of the wharf roach, Ligia exotica, inhabiting the intertidal zone of the west coast of Korea. The co-cultivation of these two strains significantly induced the production of two new metabolites, ligiamycins A (1) and B (2), which were barely detected in the single culture of Streptomyces sp. GET02.ST. The planar structures of ligiamycins A (1) and B (2) were elucidated as new decalins coupled with amino-maleimides by the analysis of various spectroscopic data, including nuclear magnetic resonance (NMR), ultraviolet (UV), and mass (MS) data. The assignment of two nitrogen atoms in amino-maleimide in 1 was accomplished based on 1H-15N heteroatom single quantum coherence spectroscopy (HSQC) NMR experiments. The relative configurations of the ligiamycins were determined using rotating frame Overhauser effect spectroscopy (ROESY) NMR data, and their absolute configurations were deduced by comparing their experimental and calculated optical rotations. Ligiamycin A (1) displayed antibacterial effects against Staphylococcus aureus and Salmonella enterica, while ligiamycin B (2) exhibited mild cell cytotoxicity against human colorectal cancer cells.

The protective effect of solidagenone from Solidago chilensis Meyen in a mouse model of airway inflammation.

Solidagenone is the main active constituent present in Solidago chilensis Meyen which is used in folk medicine to treat pain and inflammatory diseases. This study aimed to evaluate the anti-inflammatory activity of solidagenone in vitro and in a model of allergic airway inflammation. In vitro studies were performed in activated macrophages and lymphocytes. BALB/c mice were sensitized and challenged with ovalbumin and treated with solidagenone orally (30 or 90 mg/kg body weight) or dexamethasone, as a positive control in our in vivo analysis. Supernatant concentrations of nitrite, TNF and IL-1ß, as well as gene expression of pro-inflammatory mediators in macrophages cultures, were reduced after solidagenone treatment, without affecting macrophages viability. Besides, solidagenone significantly decreased T cell proliferation and secretion of IFNγ and IL-2. Th2 cytokine concentrations and inflammatory cell counts, especially eosinophils, in bronchoalveolar lavage fluid were reduced in mice treated with solidagenone. Histopathological evaluation of lung tissue was performed, and morphometrical analyses demonstrated reduction of cellular infiltration and mucus hypersecretion. Altogether, solidagenone presented anti-inflammatory activity in vitro and in vivo in the OVA-induced airway inflammation model, suggesting its promising pharmacological use as an anti-inflammatory agent for allergic hypersensitivity.

The Removal of Binary Mixture of Dyes by Heterogeneous Fenton Oxidation: Kinetics, Product Identification and Toxicity Assessment.

The removal of mixture of two azo dyes, Acid blue 29 and Ponceau xylidine, was studied by heterogeneous Fenton and Fenton-type processes using hydrogen peroxide and sodium persulphate as oxidants in the presence of and nano and micro- particles as catalysts. The synthesised nano- particles were characterised using analytical techniques viz. FT-IR, TEM, EDX, powder XRD and VSM. We have examined the effects of particle size on the COD removal efficiency and the reusability of the catalyst after optimising pH, and concentrations of catalyst and oxidant. Combination of nano-  and hydrogen peroxide possessed higher COD removal efficiency, which was accelerated in acidic pH and inhibited at pH > 6. Total consumption of hydrogen peroxide confirmed the efficiency of the optimised parameters. The mechanism of the formation of intermediate ions and products are proposed. COD removal and consumption of hydrogen peroxide follow pseudo-first-order kinetics. The toxicity of the solutions was assessed using Aliivibrio fischeri light loss and Escherichia coli growth inhibition assays. Both the assays showed different toxicity levels for the same solution.

Decorated traditional cellulose with nanoscale chiral metal-organic frameworks for enhanced enantioselective capture.

Herein, a rapid approach toward the size/morphology-controlled synthesis of [Cu(L-mal)(bipy)·2H2O] (CuLBH) was developed by adjusting the concentrations of 2-methylimidazole (2-MI) and copper ions. The chiral separation efficiency test indicated that the nano-diameter CuLBH exhibited better selective potential towards (±)-1-(1-naphthyl)ethanol (NE) by providing more fully exposed recognition sites. In order to further improve the selectivity for NE enantiomers and avoid the aggregation of MOF nanoparticles, the nanosized CuLBH-decorated carboxylated cellulose (CC) composite CC-CuLBH was designed by controlling the ratio of the solvent and Cu2+, which exhibited much higher enantioselectivity than those of pristine CC and even nano CuLBH.

Monalbidins A-E, Decalins with Potential Cytotoxic Activities from Marine Derived Fungus Monascus albidus BB3.

Five new decalins, monalbidins A-E (1, 2 and 7-9), together with 16 known compounds (3-6 and 10-21), were isolated from the AcOEt extract of marine derived fungus Monascus albidus BB3 cultured in GPY medium. Among the known compounds, 1-hydroxymonacolin L (11), dehydromonacolin J (15), 8-O-acetylmonacolin J (19) and O-acetylmonacolin K (21) were separated from natural sources for the first time. Their structures were determined by comprehensive analysis on the 1D and 2D NMR, HR-ESI-MS, UV and IR data, and their absolute configurations were assigned by experimental and calculated ECD data, and X-ray single-crystal diffraction analysis. Monalbidins C and D (7 and 8), monacolin K methyl ester (13), dehydromonacolin L (14), dehydromonacolin K (16), monacolin K (20) and O-acetylmonacolin K (21) showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, HCT116 and MDA-MB-231.

A review on chemistry, source and therapeutic potential of lambertianic acid.

Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

Anti-inflammatory naphthoates and anthraquinones from the roots of Morinda officinalis.

Morinda (Morinda officinalis) is widely consumed as a health-care herb in Asia and reported to possess various biological activities. In this study, anti-inflammatory phytochemicals were investigated and two pairs of new methyl-2-naphthoate enantiomers (1a/1b, 2a/2b), one new anthraquinone (3), three new natural unknown anthraquinones (5-6, 23), and eighteen known anthraquinones were isolated and elucidated from the roots of morinda. Anti-inflammatory activities of the isolated compounds were assessed in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compounds 2b and 19 significantly inhibited the production of NO with IC50 values of 34.32 ± 4.87 and 17.17 ± 4.13 µM (indomethacin, IC50 26.71 ± 6.32 µM), and they were further corroborated via immunoblotting, quantitative real-time PCR and immunofluorescence staining assays. They could dose-dependent suppress lipopolysaccharide-stimulated pro-inflammatory factors (COX-2 and iNOS) production and block nuclear translocation of NF-κB. The results implied that reasonable consumption of morinda may be beneficial for preventing and reducing the occurrence of inflammatory-associated diseases.

Diversity of fungal isolates from fungus-growing termite Macrotermes barneyi and characterization of bioactive compound from Xylaria escharoidea.

Owing to their potential applications, as well as their structural diversity, the discovery of novel secondary metabolites from insect-associated fungi has been of interest to researchers in recent years. The aim of this study was therefore to estimate the diversity of fungi associated with fungus-growing termites and bioprospecting these for potential secondary metabolites. In total, 18 fungal species were isolated and described from the gut and comb of Macrotermes barneyi based on 18S ribosomal DNA gene sequence analysis. Antimicrobial activity assays were carried out on all the known fungi, and nine isolates were recorded as active against pathogenic fungi. Xylaria escharoidea, the best performing isolate, was grown at laboratory scale and 4,8-dihydroxy-3,4-dihydronaphthalen-1(2H) was isolated and characterized. The minimum inhibitory concentration of this isolated compound against tested pathogenic organisms was found to be 6.25 µg. In addition, molecular docking studies have revealed that 4,8-dihydroxy-3,4-dihydronaphthalen-1(2H) is a prominent antibacterial agent with a marked interaction with key residues on protein A (agrAC ) that regulates the accessory gene. The findings of this study support the drug discovery of antimicrobial properties in insect-associated fungi, which may lead to novel secondary metabolites.

Ionic Liquid Stationary Phase for Improving Comprehensive Two-dimensional Gas Chromatographic Separation of Polychlorinated Naphthalenes.

The performance of comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC×GC-MS) using a column combination of a non-polar stationary phase (DB-5MS) and an ionic liquid stationary phase (SLB-IL60) in the first- and the second dimension has been evaluated for the suitable separation of polychlorinated naphthalenes (PCNs). The optimization of the GC×GC-MS method was carried out using different oven temperature programs and modulation conditions, achieving the best results using a ramp temperature rate of 0.75 °C min-1 and a modulation time of 12 s. Under these conditions, efficient separation of all PCN congeners present in Halowax formulations was achieved in 140 min, resolving some critical closed eluting isomers, such as CN-33/34/37, highly toxic CN-66/67 or CN-71/72 pairs, among others. These findings represent a significant improvement in the congener-specific separation of PCNs over the 1D-GC and GC×GC methodologies already published and the DB-5MS × SLB-IL60 column combination offered the orthogonality required for the congener-specific determination with a high peak capacity. The GC×GC-MS method was applied to the characterisation of Halowax formulations, obtaining similar compositional profiles than those previously reported.

Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models.

Solidagenone (SOL) is a labdane-type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti-inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil-, arachidonic acid (AA)- and phenol-induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-ß-dehydrogenase and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton oil-, AA- and phenol-induced ear oedema (P < .001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and TNF-α, IL-6 and NO levels were decreased (P < .001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0 mg/ear. The docking study showed that SOL interacts with COX-1 and prostaglandin-E(2)-9-reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti-inflammatory agent.

Hatsusamides A and B: Two New Metabolites Produced by the Deep-Sea-Derived Fungal Strain Penicillium steckii FKJ-0213.

Two new nitrogen-containing metabolites, designated hatsusamide A (1) and B (2), were isolated from a culture broth of Penicilliumsteckii FKJ-0213 together with the known compounds tanzawaic acid B (3) and trichodermamide C (4) by physicochemical (PC) screening. The structures of 1 and 2 were determined as a tanzawaic acid B-trichodermamide C hybrid structure and a new analog of aspergillazines, respectively. The absolute configuration of 1 was determined by comparing the values of tanzawaic acid B and trichodermamide C in the literatures, such as 1H-nuclear magnetic resonance (1H-NMR) data and optical rotation, after hydrolysis of 1. Compounds 1-4 were evaluated for cytotoxicity and anti-malarial activities. Compounds 1 and 3 exhibited weak anti-malarial activity at half-maximal inhibitory concentration (IC50) values of 27.2 and 78.5 µM against the K1 strain, and 27.9 and 79.2 µM against the FCR3 strain of Plasmodium falciparum, respectively. Furthermore, 1 exhibited cytotoxicity against HeLa S3, A549, Panc1, HT29 and H1299 cells, with IC50 values of 15.0, 13.7, 12.9, 6.8, and 18.7 µM, respectively.

N-doped mesoporous carbon as a new sorbent for ultrasonic-assisted dispersive micro-solid-phase extraction of 1-naphthol and 2-naphthol, the biomarkers of exposure to naphthalene, from urine samples.

This study aimed to optimize a new sample preparation method using N-doped mesoporous carbon sorbent for simultaneous measurement of 1-naphthol and 2-naphthol, the biomarkers of exposure to naphthalene. The samples were analyzed using high-performance liquid chromatography supplied with ultraviolet detector (HPLC-UV). N-doped mesoporous carbon sorbent was obtained via the hard template procedure. The synthesized nanosorbent was then characterized by transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), and elemental analysis (CHN). The effective factors in the extraction of the studied biomarkers were examined by the Box-Behnken (BBD) methodology. Regarding the optimum conditions, the sketched calibration curve for naphthols was linear in the concentration levels of 1-600 µg L-1 for human urine samples. The accuracy and reproducibility of the introduced method were determined using the relative recovery (RR %) and relative standard deviation (RSD %) tests on the fortified urine samples. RR% and RSD% were found to be 97.0-101.2% and 3.1-9.0%, respectively. The calculated method detection limit of the optimized procedure was 0.3 µg L-1 and 0.5 µg L-1 for 1-naphthol and 2-naphthol, respectively.

Electrochemically deposition of ionic liquid modified graphene oxide for circulated headspace in-tube solid phase microextraction of naphthalene from honey samples followed by on-line liquid chromatography analysis.

In this work, an inexpensive, fast, and selective ionic liquid modified graphene oxide (GO-IL) was synthesized and electrochemically deposited on the inner surface of a stainless-steel tube. Then, it was applied for circulated headspace in-tube solid-phase microextraction (CHS-IT-SPME) of naphthalene from honey samples. Next, the coated tube was replaced with the sample loop of a six-port injection valve for on-line desorption and further HPLC-UV analysis of naphthalene. The sorbent was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and energy-dispersive X-ray spectroscopy (EDX). Different parameters affecting the procedure efficiency, including extraction temperature, extraction time, salt concentration, and sample volume were optimized by central composite design and response surface methodology. Under the optimum conditions, the calibration curve was linear within the range of 0.3-200 ng mL-1, with a regression coefficient of 0.9972. The limits of detection (LOD) and quantification (LOQ) were found to be 0.1 ng mL-1 and 0.3 ng mL-1, respectively. Intra-day and inter-day RSDs% for three replicate measurements of naphthalene at the concentration of 10 ng mL-1 were obtained 3.9% and 5.0%, respectively. Also, good tube-to-tube reproducibility of 5.3% was achieved. Finally, the method was successfully applied for measuring trace amounts of naphthalene in honey samples. Relative recoveries were calculated within the range of 90.0-106.5%, indicating excellent efficiency of the proposed method.

Chemical Constituents from Endophytic Fungus Annulohypoxylon cf. stygium in Leaves of Anoectochilus roxburghii.

The chemical investigation on endophytic fungus Annulohypoxylon cf. stygium in leaves of Anoectochilus roxburghii (Wall.) Lindl. has been performed. Sixteen compounds were isolated and their structures were identified as (-)-notoamide A, (-)-notoamide B, (+)-versicolamide B, notoamide C, notoamide D, stephacidin A, sterigmatocystin, dihydrosterigmatocystin, secosterigmatocystin, versiconol, averufanin, kipukasin D, kipukasin E, diorcinal, palmarumycin CP2 and (-)-(3R)-mellein methyl ether, respectively, by spectroscopic analysis and comparison with literature data. All the compounds were isolated from Annulohypoxylon genus for the first time. Sterigmatocystin and palmarumycin CP2 showed selective cytotoxic activities against HepG2, HeLa, MCF-7 and HT-29.

High performance liquid chromatography - Mass spectrometric bioanalytical method for the determination of dapoxetine in human plasma: Application for bioequivalence study.

Dapoxetine is an oral medication used for treatment of premature ejaculation (PE) in men aged (18-64 years). In this study, we present a validated, precise and sensitive method for determination of dapoxetine in human plasma by liquid chromatography/ electrospray ionization-tandem mass spectrometry. Dapoxetine and the internal standard (Dapoxetine- d6) were extracted from plasma via liquid-liquid extraction (LLE). The LC separation was performed utilizing ACE C8 (4.6 X50) mm, 5 µm column. The mobile phase was composed of acetonitrile and buffer (0.01 M Ammonium acetate +0.02% Formic acid solution) (85:15, v/v). The method was linear within the concentration range of 5.0-600 ng/mL for Dapoxetine in human plasma. Short analytical run was achieved with 1.6 min run time. Intra-day and inter-day accuracy was between 97 and 106% with precision (CV, %) of ≤ 5% achieved across all the quality control samples. Dapoxetine was stable in several conditions with recovery rates > 90%. This method was utilized successfully in clinical pharmacokinetic study following oral administration of 60 mg Dapoxetine tablets in 36 healthy male subjects. The result for all 90% confidence intervals were within the preset ranges. The method proved to be highly reproducible and sensitive and thus can be employed in bioequivalence studies and large scale sample analysis of Dapoxetine.

Naphthalenones and Naphthols Isolated from the Saussurea laniceps Endophytic Fungus Didymella glomerata X223.

One new naphthalenone, didymelol A, and three new naphthols, didymelol B-D, together with three known naphthalenones, (3S,4R)-3,4,6-trihydroxy-3,4-dihydronaphthalen-1(2H)-one, (4S)-4,6-dihydroxy-3,4-dihydronaphthalen-1(2H)-one, (4S)-4-hydroxy-3,4-dihydronaphthalen-1(2H)-one, were isolated from the Saussurea laniceps endophytic fungus Didymella glomerata X223. The structures of the isolates were elucidated based on extensive spectroscopic data analysis. The absolute configuration of didymelol A was established through single-crystal X-ray diffraction data and didymelols B-D were identified through comparisons of experimental and calculated ECD spectra. All compounds were evaluated for cytotoxic activity against human non-small cell lung cancer A549 cells and human breast carcinoma MDA-MB-435 cells.

Julichrome Monomers from Marine Gastropod Mollusk-Associated Streptomyces and Stereochemical Revision of Julichromes Q3 ⋠5 and Q3 ⋠3.

Two julichrome monomers, julichromes Q11 (1) and Q12 (2), along with five known julichromes (Q10 , Q3 ⋅ 5 , Q3 ⋅ 3 , Q6 ⋅ 6 , Q6 , 3-7) and four known anthraquinones (chrysophanol, 4-acetylchrysophanol, islandicin, huanglongmycin A, 8-11), were isolated from the marine gastropod mollusk Batillaria zonalis-associated Streptomyces sampsonii SCSIO 054. This is the first report of julichromes isolated from a marine source. Extensive dissection of 1D and 2D NMR datasets combined with X-ray crystallography enabled rigorous elucidation of the previously reported configurations of julichrome Q3 ⋅ 5 (4) and related julichrome Q3 ⋅ 3 (5); both of the configuration at C(9) needs to be revised. In addition, julichrome Q12 (2) was found to display antibacterial activity against Micrococcus luteus and Bacillus subtilis with MICs of 2.0 and 8.0 µg mL-1 ; four compounds (1, 3, 6, 7) also showed inhibitory activities against an array of methicillin-resistant Staphylococcus aureus, S. aureus and S. simulans AKA1 with MIC values ranging from 8 to 64 µg mL-1 .

Microaerated UASB reactor treating textile wastewater: The core microbiome and removal of azo dye Direct Black 22.

Sequential anaerobic and aerobic processes have been recommended to treat textile wastewater reliably. In this work, the focus was on finding an energetically more competitive system to remove tetra-azo dye Direct Black 22 (DB22). We operated two upflow anaerobic sludge blanket (UASB) reactors (R1 and R2) in three phases (PI, PII, and PIII). R1 was operated as a conventional UASB, while R2 was microaerated in the upper part (0.18 ±â€¯0.05 mg O2. L-1), aiming to remove DB22 simultaneously with the aromatic amine byproducts. PI consisted of feeding reactors with synthetic textile wastewater (STW), PII had higher salinity in the STW, and PIII was the same as PII, plus sulfate. The results showed that color and COD removal efficiencies were similar for both reactors (67-72% for R1 and 59-78% for R2) without a substantial influence of oxygen in R2. However, microaeration played a crucial role in R2 by removing the anaerobically formed aromatic amines; during PIII, the effluent was 16 times less toxic than that of R1. The microbial community that developed in the sludge bed of both reactors was quite similar, with the core microbiome represented by Trichococcus, Syntrophus and Methanosaeta genera. The increase in salinity in PII and PIII promoted a shift in the microbial community, excluding salty-sensitive genera from the core microbiome. The putative genera Brevundimonas and Ornatilinea were associated to aromatic amine microaerobic removal. Therefore, there is a potential application of a compact microaerated anaerobic system for textile wastewater treatment.

Racemic 3,4-dihydro-4-naphthyl-naphthalen-1(2H)-ones from Juglans regia flowers.

Three previously undescribed (±)-3,4-dihydro-4-naphthyl-naphthalen-1(2H)-one derivatives were isolated from Juglans regia flowers. Elucidation of the 2D structures of these first-reported compounds was completed via regular spectroscopic methods. The assignment of racemic nature of these compounds was achieved using the examination of their chiral HPLC profiles. (±)-2,3-Dihydro-4',8,8'-trihydroxy-(1,1'-binaphthalen)-4(1H)-one, (±)-2,3-dihydro-4',5,8,8'-tetrahydroxy-(1,1'-binaphthalen)-4(1H)-one, and (±)-2,3-dihydro-1',5,5',8-tetrahydroxy-(1,2'-binaphthalen)-4(1H)-one were the structures of these racemic compounds, all taking on central chirality. The resolution of all the racemic compounds was conducted and achieved using a chiral HPLC procedure. The absolute configurations of the three isolated pairs of enantiomers were assigned via time-dependent density functional theory calculations from the electronic circular dichroism data. The findings in this paper demonstrated that the relevant biochemical reactions for the construction of these 3,4-dihydro-4-naphthyl-naphthalen-1(2H)-one derivatives in the test plant are nonselective. The (±)-2,3-dihydro-4',8,8'-trihydroxy-(1,1'-binaphthalen)-4(1H)-one showed selective inhibitory activity on tumor cells growth, preliminarily supporting the application of Juglans regia flowers to protect against cancers in a few Chinese folk areas.

Sparticolins A-G, Biologically Active Oxidized Spirodioxynaphthalene Derivatives from the Ascomycete Sparticola junci.

To explore the chemical diversity of metabolites from new species of Dothideomycetes, the ex-type strain of Sparticola junci was investigated. Seven highly oxygenated and functionalized spirodioxynaphthalene natural products incorporating carboxyalkylidene-cyclopentanoid (1-4), carboxyl-functionalized oxabicyclo[3.3.0]octane (5-6), and annelated 2-cyclopentenone/δ-lactone (7) units, sparticolins A-G, were isolated from submerged cultures of the fungus. Their chemical structures including their relative (and absolute) configurations were established through spectroscopic and X-ray crystallographic analyses. Sparticolin B (2) exhibited inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus, while sparticolin G (7) showed antifungal activities against Schizosaccharomyces pombe and Mucor hiemalis. All other sparticolins were only weakly active against S. aureus and also showed weak activities against the nematode Caenorhabditis elegans. Compounds 2 and 7 also showed moderate cytotoxic activities against seven mammalian cell lines.