Effect of Cd<Superscript>+2</Superscript> on phosphate solubilizing abilities and hydrogen peroxide production of soil-borne micromycetes isolated from <Emphasis Type="Italic">Phragmites australis</Emphasis>-rhizosphere

The aims of this work were to evaluate the phosphate-solubilization and hydrogen peroxide (H₂O₂) production by the soil-borne micromycetes, Aspergillus japonicus, Penicillium italicum and Penicillium dipodomyicola, isolated from Phragmites australis rhizosphere and to study the effect of several concentrations of Cadmium (Cd²⁺) on both variables. Our results showed that P. italicum achieved a higher P-solubilization and H₂O₂ production than A. japonicus and P. dipodomyicola, as only P. italicum showed a positive correlation (R² = 0.71) between P-solubilization and H₂O₂ production. In dose–response assays, P. italicum was also more tolerant to Cd²⁺ (0.31 mM) in comparison to A. japonicus (0.26 mM). Analysis of the 2⁴ factorial experimental design showed that P-solubilization by P. italicum was negatively affected by increases in Cd²⁺ (p = 0.04) and yeast extract (p = 0.02) in the culture medium. The production of H₂O₂ was positively affected only by glucose (p = 0.002). Fungal biomass production was reduced significantly (p = 0.0009) by Cd²⁺ and increased (p = 0.0003) by high glucose concentration in the culture medium. The tolerance and correlation between P-solubilization and H₂O₂ production in the presence of Cd²⁺ was strain and species dependent. The effects of Cd²⁺, glucose, ammonium sulfate and yeast extract on those variables were evaluated through a two-level factorial design. P. italicum is promising for P-solubilization in soils contaminated with Cd²⁺ and may be an alternative for manufacture of biofertilizers to replace chemical fertilizers.     

Synthesis of novel triazolyl pyranochromen-2(1<Emphasis Type="Italic">H</Emphasis>)-ones and their antibacterial activity evaluation

A series of thirty-three novel triazolyl pyranochromen-2(1H)-one derivatives have been synthesized via Cu (I) catalysed Huisgen 1,3-dipolar cycloaddition reaction. All of the synthesized compounds have been fully characterized from their spectral data and evaluated for antibacterial activity against both gram-positive and gram-negative bacteria. The activity results revealed that amongst all the compounds screened, six compounds, i.e. 2-[4-(((7-ethyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid (41), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-3-ethyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (44), 3-ethyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (46), 2-[4-(((7-hexyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid (52), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-3-hexyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (55) and 3-hexyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (57), exhibited moderate activity against all the strains studied with zone of inhibition between 10 and 16 mm and MIC values in the range of 75–170 µg/mL as compared to the standard used. The information obtained from structure–activity relationship can be used to design and develop the next generation of compounds with higher antibacterial efficacy.     

C<Subscript>21</Subscript> steroid derivatives from the Dai herbal medicine Dai-Bai-Jie,the dried roots of <Emphasis Type="Italic">Marsdenia tenacissima</Emphasis>, and their screening for anti-HIV activity

Twenty-three new C₂₁ steroidal glycosides, marstenacissides C1–C10 (1–10), D1–D7 (11–17) and E1–E6 (18–23), and four new C₂₁ steroids, 11α,12β-O-ditigloyl-tenacigenin C (24), 11α-O-benzoyl-12β-O-tigloyl-tenacigenin C (25), 11α-O-tigloyl-12β-O-benzoyl-tenacigenin C (26) and 11α-O-tigloyl-12β-O-benzoyl-marsdenin (27), were isolated from the Dai herbal medicine Dai-Bai-Jie, derived from the roots of Marsdenia tenacissima. The chemical structures of all compounds were established by spectroscopic techniques, including high-resolution mass spectrometry and NMR spectroscopy, as well as by comparison with reported spectral data. The anti-HIV activities of these compounds were screened, and the compounds obtained displayed inhibitory effects against HIV-1 with inhibition rates of 36.4–81.3% at 30 μM.     

Antioxidant <Emphasis Type="Italic">C</Emphasis>-glycosylflavones of <Emphasis Type="Italic">Drymaria cordata</Emphasis> (Linn.) Willd

A new C-glycosylflavone, drymaritin E (6-C-(3-keto-β-digitoxopyranosyl)-4′-O-(β-d-glucopyranosyl)-7-methoxyl-5,4′-dihydroxylflavone) 1 was isolated from the oily upper phase (SU) of the MeOH extract from aerial parts of Drymaria cordata together with two known compounds (cassiaoccidentalin A 2 and anemonin 3) and an inseparable mixture of two known C-glycosylflavones 5,4′-dihydroxy-7-methoxyflavone-6-C-(2′′-O-α-l-rhamnopyranosyl)-β-d-glucopyranoside 4a and 5,7,3′,4′-tetrahydroxyflavone-6-C-(2′′-O-α-l-rhamnopyranosyl)-β-d-glucopyranoside 4b. The alkaline hydrolysis of 3 led to a new hemisynthetic derivative, sodium anemonate (sodium 2-((1’E) 2′-sodium-carboxylate-vinyl)-5-oxo-cyclohex-1-ene carboxylate) 3a. The chemical structures were determined by spectroscopic methods (¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMBC, HSQC, and NOESY) and mass spectrometry (ESI–MS). C-glycosylflavones had significant free radical-scavenging activities on the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). However, SU and compounds 3 and 3a exhibited no activity. In particular, compound 1 exhibited a concentration-dependent radical scavenging activity on DPPH with EC₅₀ of 31.43 µg/mL.     

Three new <Emphasis Type="Italic">C</Emphasis>-glycosyflavones with acetyl substitutions from <Emphasis Type="Italic">Swertia mileensis</Emphasis>

Three new acetylated C-glycosylflavones, 3″,6″-di-O-acetylswertiajaponin (1), 4″,6″-di-O-acetylswertiajaponin (2), and 6″-O-acetylswertiajaponin (3), together with six known compounds were isolated from the whole herb of Swertia mileensis. Their structures were elucidated on extensive NMR experiments and mass spectrometry studies. ¹H and ¹³C NMR data exhibited doublet signals at room temperature. Variable temperature ¹H NMR experiments were carried out to investigate the presence of rotational isomerism of C-glycosylflavones. All compounds showed potential antioxidant activities against apoptosis of H₂O₂-induced human embryo liver L02 cells.     

Identification of <Emphasis Type="Italic">N</Emphasis>-arylsulfonylpyrimidones as anticancer agents

For confirming the role of five membered ring of imidazolidinone moiety of N-arylsulfonylimidazolidinones (7) previously reported with highly potent anticancer agent, a series of N-arylsulfonylpyrimidones (10a–g) and N-arylsulfonyltetrahydropyrimidones (11a–e) were prepared and their anti-proliferating activity was measured against human cancer cell lines (renal ACHN, colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3) using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4-phenyltetrahydropyrimidin-2(1H)-one (11d, mean GI₅₀ = 3.50 µM) and ethyl 5-(2-oxo-4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean GI₅₀ = 0.26 µM) showed best growth inhibitory activity against human cancer cell lines. Considering the activity results, N-arylsulfonyltetrahydropyrimidones (11) exhibited more potent activity compared to N-arylsulfonylpyrimidones (10) and comparable activity to N-arylsulfonylimidazolidinones (7). Especially, tetrahydropyrimidin-2(1H)-one analogs containing acylindolin-5-ylsulfonyl moiety at position 1 demonstrated their strong growth inhibitory activity against human cancer cell lines.     

Alkyl phenols,alkenyl cyclohexenones and other phytochemical constituents from <Emphasis Type="Italic">Lannea rivae</Emphasis> (chiov) Sacleux (Anacardiaceae) and their bioactivity

Six novel compounds, 3-nonadec-14′-(Z)-enyl phenol (1a); 4,5-dihydroxy-4,2′-epoxy-5-[16′-Z-18′-E-heneicosenyldiene]-cyclohex-2-enone (2), 2,4,5-trihydroxy-2-[16′-Z-heneicosenyl]-cyclohexanone (3); 4S,6R-dihydroxy-6-[12′-Z-heptadecenyl]-cyclohex-2-enone (4a); 4S,6R-dihydroxy-6-[14′-Z-nonadecenyl]-cyclohex-2-enone (4b); and 1,2,4-trihydroxy-4-[16′-Z-heneicosenyl]-cyclohexane (5) were identified from the roots and stems of Lannea rivae in addition to the known cardanols, 3-heptadec-12′-Z-enyl phenol (1b), 3-pentadec-10′-Z-enyl phenol (1c) and 3-pentadecyl phenol (1d), sitosterol (6), sitosterol glucoside (7), taraxerone (8), taraxerol (9), E-lutein (10), myricetin (11), myricetin-3-O-α-rhamnopyranoside (12), myricetin-3-O-β-galactopyranoside (13) and (-)-epicatechin-3-O-gallate (14). The ketones 4a and 4b were isolated as a mixture and were qualitatively separated and identified by GCMS. Myricetin (11) and epicatechin gallate (14) displayed over 90 % DPPH radical-scavenging activity at 50 μg mL^?1, while its glycosides (12 and 13) showed percentages of over 70 % in the same assay. The same compounds 11 and 14 showed antibacterial activity similar to erythromycin and vancomycin against Gram-positive bacteria and were also active against Gram-negative bacteria, but not as much as the cefuroxime, ciprofloxacin and nalidixic acid standards. Compounds 1a–d, 4a–b and 5 were all relatively non-toxic, while 2 (the epoxy cyclohex-2-enone) and 3 (the trihydroxy cyclohexanone) showed more toxicity than the others. These two toxic compounds, 2 and 3 also showed antiplasmodial activity with IC₅₀ values between 0.48 and 2.05 μg mL^?1. The mixture of dihydroxy cyclohex-2-enones 4a and 4b, which was far less toxic than 2 and 3, also showed promising antiplasmodial activity and may be a possible lead for further investigation as an antiplasmodial drug.     

Synthesis,biological evaluation,and molecular modeling of (<Emphasis Type="Italic">E</Emphasis>)-2-aryl-5-styryl-1,3,4-oxadiazole derivatives as acetylcholine esterase inhibitors

A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a–o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a–q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC₅₀ values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein–ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives.     

Degranulation inhibitors from the arils of <Emphasis Type="Italic">Myristica fragrans</Emphasis> in antigen-stimulated rat basophilic leukemia cells

A methanol extract of mace, the aril of Myristica fragrans (Myristicaceae), was found to inhibit the release of β-hexosaminidase, a marker of antigen-IgE-stimulated degranulation in rat basophilic leukemia cells (RBL-2H3, IC₅₀ = 45.7 μg/ml). From the extract, three new 8-O-4′ type neolignans, maceneolignans I–K (1–3), were isolated, and the stereostructures of 1–3 were elucidated based on spectroscopic and chemical evidence. Among the isolates, maceneolignans A (5), D (6), and H (8), (?)-(8R)-?^8′-4-hydroxy-3,3′,5′-trimethoxy-8-O-4′-neolignan (13), (?)-(8R)-?^8′-3,4,5,3′,5′-pentamethoxy-8-O-4′-neolignan (14), (?)-erythro-(7R,8S)-?^8′-7-acetoxy-3,4-methylenedioxy-3′,5′-dimethoxy-8-O-4′-neolignan (17), (+)-licarin A (20), nectandrin B (24), verrucosin (25), and malabaricone C (29) were investigated as possible degranulation inhibitors (IC₅₀ = 20.7–63.7 μM). These inhibitory activities were more potent than those of the antiallergic agents tranilast (282 μM) and ketotifen fumalate (158 μM). Compounds 5, 25, and 29 also inhibited antigen-stimulated tumor necrosis factor-α production (IC₅₀ = 39.5–51.2 μM), an important process in the late phase of type I allergic reactions.     

<Emphasis Type="Italic">Apium graveolens</Emphasis> extract influences mood and cognition in healthy mice

Apium graveolens is a food flavoring which possesses various health promoting effects. This study investigates the effect of a sub-acute administration of A. graveolens on cognition and anti-depression behaviors via antioxidant and related neurotransmitter systems in mice brains. Cognition and depression was assessed by various models of behavior. The antioxidant system of glutathione peroxidase (GPx), % inhibition of superoxide anion (O₂ ^?), and lipid peroxidation were studied. In addition, neurochemical parameters including acetylcholinesterase (AChE) and monoamine oxidase-type A (MAO-A) were also evaluated. Nine groups of male mice were fed for 30 days with different substances—a control, vehicle, A. graveolens extract (65–500 mg/kg), and reference drugs (donepezil and fluoxetine). The results indicated that the effect of the intake of A. graveolens extract (125–500 mg/kg) was similar to the reference drugs, as it improved both spatial and non-spatial memories. Moreover, there was a decrease in immobility time in both the forced swimming and tail suspension tests. In addition, the A. graveolens extract reduced lipid peroxidation of the brain and increased GPx activity and the % inhibition of O₂ ^?, whereas the activities of AChE and MAO-A were decreased. Thus, our data have shown that the consumption of A. graveolens extract improved cognitive function and anti-depression activities as well as modulating the endogenous antioxidant and neurotransmitter systems in the brain, resulting in increased neuronal density. This result indicated an important role for A. graveolens extract in preventing age-associated decline in cognitive function associated with depression.     

Chemical composition and bioactivities of the essential oil from different organs of <Emphasis Type="Italic">Ferula communis</Emphasis> L. growing in Tunisia

The essential oils obtained by the hydrodistillation from the fresh flowers, leaves, stems, and roots of Ferula communis L., growing in Tunisia were analyzed by GC and GC/MS. Thirty-two components were identified in the oil of flowers with camphor (18.3 %), α-pinene (15.3 %), and β-eudesmol (9.3 %) as the main constituents. Twenty-nine compounds were identified in the oil of stems with β-eudesmol (28.1 %), δ-eudesmol (11.1 %), and α-eudesmol (9.6 %) as the main compounds. Twenty compounds were characterized in the oil of roots with dillapiole (7.9 %), guaiol (7.3 %), and spathulenol (6.8 %). In the oil of leaves, α-eudesmol (25.2 %), β-eudesmol (20.7 %), δ-eudesmol (10.1 %), and caryophyllene oxide (7.2 %) were found as the main constituents. This study was undertaken to evaluate the antioxidant activity using DPPH (2,2′-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid), reducing power, and catalase activity. We tested also the antibacterial, cytotoxic, and cholinesterase inhibition properties of the essential oil of different organs of F. communis. The essential oil of the stems showed the highest antioxidant activity (IC₅₀ = 0.03 ± 0.001 mg mL^?1), in DPPH assay and the important result of catalase (303.03 µmol H₂O₂ degraded/min/protein) of F. communis. The antibacterial activity of the oil was determined by micro-well dilution assay. The best results (MIC = 0.156 ± 0.02 mg mL^?1) were exhibited by the essential oil of the leaves of F. Communis against Pseudomonas aeruginosa. Besides, the strongest cytotoxic activity against Hela cells was shown with essential oils’ leaves with an inhibition percentage of 79.05 % at the concentration of 500 µg mL^?1. However, the best inhibition percentage of A 549 cells was detected for essential oils’ leaves with an inhibition percentage of 54.56 % at 250 µg mL^?1. Our finding showed that the essential oil of the flowers was the most active, with 64.623 % of inhibition against butyrylcholinesterase at 10 mg mL^?1 from the incubation time of 30 min.     

A new indole glycoside from the seeds of <Emphasis Type="Italic">Raphanus sativus</Emphasis>

A new indole glycoside, β-d-glucopyranosyl 2-(methylthio)-1H-indole-3-carboxylate, named raphanuside A (1), as well as eight known compounds, β-d-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-d-glucopyranoside (2), (3-O-sinapoyl)-β-d-fructofuranosyl-(2 → 1)-α-d-glucopyranoside (3), (3-O-sinapoyl)-β-d-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-d-glucopyranoside (4), (3,4-O-disinapoyl)-β-d-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-d-glucopyranoside (5), isorhamnetin 3,4′-di-O-β-d-glucoside (6), isorhamnetin 3-O-β-d-glucoside-7-O-α-l-rhamnoside (7), isorhamnetin 3-O-β-d-glucoside (8) and 3'-O-methyl-(?)-epicatechin 7-O-β-d-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1–3 and 6–9, were isolated from this plant for the first time. The structures of compounds 1–9 were identified using 1D and 2D NMR, including ¹H–¹H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-α stimulated MG-63 cells was also examined.     

Effect of Gastric Fluid Volume on the <Emphasis Type="Italic">In Vitro</Emphasis> Dissolution and <Emphasis Type="Italic">In Vivo</Emphasis> Absorption of BCS Class II Drugs: a Case Study with Nifedipine

Nifedipine is a BCS Class II drug used for treatment of hypertension and preterm labor. Large inter-patient variability in nifedipine absorption results in variable exposure among different patients. We conducted in vitro dissolution studies to compare nifedipine dissolution from immediate release (IR) capsules with different volumes of dissolution media. Results from dissolution studies were used to design a crossover study in healthy volunteers to evaluate the effect of coadministered water volume with nifedipine 10 mg IR capsules on nifedipine pharmacokinetics, especially absorption (C _max, t _max, and AUC_0-6). Dissolution studies demonstrated that larger gastric fluid volumes result in enhanced nifedipine dissolution from 10 mg IR cosolvent capsules (73 vs. 17% in 200 and 100 mL simulated gastric fluid, respectively, at 30 min). The pharmacokinetic crossover study in healthy volunteers (N?=?6) did not show a significant effect of the water volume administered with the capsule (50 vs. 250 mL) on C _max, t _max, or AUC_0-6 of orally administered nifedipine IR capsules (10 mg). However, administration of large water volumes resulted in lower variability in nifedipine C _max (47 vs. 70% for 250 and 50 mL, respectively). Administration of large water volumes with nifedipine 10 mg IR cosolvent capsules may reduce inter-individual variability in plasma exposure. Evaluation of similar effects in other BCS Class II drugs is recommended.     

<Emphasis Type="Italic">Rubus imperialis</Emphasis> (Rosaceae) extract and pure compound niga-ichigoside F1: wound healing and anti-inflammatory effects

Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H₂O₂-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined. The data obtained show that the extract of R. imperialis promote reduction in the inflammatory process induced by lipopolysaccharide (LPS) or carrageenan in the air pouch model; the effects could be reinforced by nitric oxide reduction in LPS-stimulated neutrophils, and an increase in the efferocytosis. The extract showed wound healing property in vitro and in vivo, scavenging activity for DPPH, and cytoprotection in the H₂O₂-induced oxidative stress in L929 cells. In addition, the compound niga-ichigoside F1 was able to reduce the NO secretion; however, it did not present wound-healing activity in vitro. Together, the data obtained point out the modulatory actions of R. imperialis extract on leukocyte migration to the inflamed tissue, the antioxidant, and the pro-resolutive activity. However, the R. imperialis anti-inflammatory activity may be mediated in parts by niga-ichigoside F1, and on wound healing do not correlated with niga-ichigoside F1.     

Synthesis and biological evaluation of some functionalized 1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole tethered pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridin-6(7<Emphasis Type="Italic">H</Emphasis>)-ones as antimicrobial and apoptosis inducing agents

A series of novel molecular hybrids containing pyrazole, pyridinone and 1,2,3-triazoles have been synthesized by one-pot four-component reaction of Meldrum’s acid, substituted aryl azides, 4-(prop-2-yn-1-yloxy)aryl aldehyde and 3-methyl-1-phenyl-1H-pyrazol-5-amine using L-proline as a basic organocatalyst besides CuSO₄.5H₂O and sodium ascorbate as catalysts for click chemistry in PEG-400 as a highly efficient and green media. Apoptosis studies have been carried out on ovarian follicles of goat (Capra hircus) and in vitro antibacterial activity has been done against six strains namely Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa and antifungal activity against two yeast strains namely, Candida albicans and Saccharomyces cerevisiae.     

In vitro antimicrobial and acetylcholinesterase inhibitory activities of coumarins from <Emphasis Type="Italic">Ferulago</Emphasis><Emphasis Type="Italic">carduchorum</Emphasis>

Ferulago carduchorum (Apiaceae) is an endemic plant of Iran. From the hexane and ethyl acetate extracts of F. carduchorum seven coumarins, one flavonoid and one steroid were isolated using column chromatography with silica gel and Sephadex LH₂₀ as the stationary phases. Antimicrobial activity of the isolated compounds was examined by a broth microdilution method. Acetylcholinesterase (AChE) inhibitory activity of isolated coumarins was also investigated. The isolated compounds were identified as suberosin, suberenol, bergapten, xanthotoxin, isopimpinellin, prantschimgin, β-sitosterol and hesperetin by comparison of their NMR and MS spectral data with those reported in the literature. Evaluation of the minimum inhibitory concentration (MIC) for each compound showed that hesperetin (flavonoid) was the most potent antimicrobial agent against a gram-positive bacterium (Staphylococcus aureus) and among the coumarins, bergapten had the best activity against S. aureus and Candida albicans. All coumarins inhibited AchE enzyme, in which xanthotoxin showed the most inhibitory among them (IC₅₀ = 39.64 µM). Our results indicate that isolated coumarins are effective against the tested bacterial strains and have AchE inhibitory activity suggesting their potential for commercial applications.     

Bt<Subscript>i</Subscript>-based insecticide enhances the predatory abilities of the backswimmer <Emphasis Type="Italic">Buenoa tarsalis</Emphasis> (Hemiptera: Notonectidae)

The backswimmer Buenoa tarsalis (Hemiptera: Notonectidae) is a naturally occurring predator of immature stages of mosquitoes. These aquatic predators can suffer from non-targeted exposure to insecticides that are commonly used in aquatic environments to control mosquitoes. Here, we evaluated whether insecticide formulations containing the bacterium Bacillus thuringiensis var. israelensis (Bt_i) or the organophosphate pirimiphos-methyl would affect the survival and the predatory abilities of B. tarsalis. First, we conducted survival bioassays to estimate the median survival time (LT₅₀) of B. tarsalis when exposed to Bt_i-based insecticide (at 0.25 and 25?mg a.i./L) and pirimiphos-methyl (at 1, 10 and 1000?mg a.i./L). The highest concentrations of the insecticides were equivalent to the label-recommended field rates. Second, the predatory abilities of B. tarsalis exposed to insecticides were evaluated at three prey densities (3, 6 and 9 mosquito larvae/100?mL water) just after insecticide exposure or after a 24?h recovery time. While the survival of B. tarsalis was significantly reduced with pirimiphos-methyl concentrations ≥10?mg a.i./L, the Bt_i-exposed predators exhibited similar survival as unexposed predators. Interestingly, after a recovery time of 24?h, B. tarsalis sublethally exposed to pirimiphos-methyl or Bt_i-based insecticide consistently killed more A. aegypti larvae (at the intermediate density) than unexposed predators. However, for the without-recovery bioassays, the pirimiphos-methyl-exposed predators exhibited reduced predatory abilities at the lowest prey density. Because they do not reduce the survival or the predatory abilities of B. tarsalis, Bt_i-based insecticides can be considered a safe insecticide to use in the presence of backswimmers.     

Effects of <Emphasis Type="Italic">CYP2C9</Emphasis> genetic polymorphisms on the pharmacokinetics of zafirlukast

Zafirlukast, a cysteinyl leukotriene receptor antagonist, is indicated for the treatment of patients with mild to moderate asthma. Zafirlukast is metabolized mainly by CYP3A4 and CYP2C9. We investigated the effects of the major CYP2C9 variant alleles in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of zafirlukast in healthy Korean subjects. A single 20-mg oral dose of zafirlukast was given to 23 Korean male subjects divided into two genotype groups according to CYP2C9 genotypes, CYP2C9EM (n = 11; CYP2C9*1/*1) and CYP2C9IM (n = 12; 9 and 3 carriers of CYP2C9*1/*3 and *1/*13, respectively). Zafirlukast concentrations were determined using a validated HPLC–MS/MS analytical method in plasma samples collected after the drug intake. Compared with the CYP2C9EM group, the C_max and AUC_inf of zafirlukast in the CYP2C9IM group were 1.44- and 1.70-fold higher, respectively (p < 0.01 and p < 0.0001). The CL/F of zafirlukast was 42.8 % lower in the CYP2C9IM group compared with the CYP2C9EM group (p < 0.001). Slightly higher C_max and AUC, and lower CL/F of zafirlukast were observed in subjects with the CYP2C9*1/*13 genotype compared with the CYP2C9*1/*3 genotype subjects. CYP2C9*3 and CYP2C9*13 alleles significantly affected the plasma concentrations of zafirlukast.     

Two new naphthalenic lactone glycosides from <Emphasis Type="Italic">Cassia obtusifolia</Emphasis> L. seeds

Two new naphthalenic lactone glycosides, (3S)-9,10-dihydroxy-7-methoxy-3-methyl-1-oxo-3,4-dihydro-1H-benzo[g]isochromene-3-carboxylic acid 9-O-β-d-glucopyranoside (1) and (3R)-cassialactone 9-O-β-d-glucopyranoside (2) were isolated from seeds of Cassia obtusifolia Linn., along with five known compounds: (3R)-cassialactone 9-O-β-d-gentiobioside (3), emodin 1-O-β-gentiobioside (4), 1-hydroxyl-2-acetyl-3,8-dimethoxy-naphthalene 6-O-β-d-apiofuranosyl-(1?→?2)-β-d-glucopyranoside (5), rubrofusarin 6-O-β-d-gentiobioside (6), rubrofusarin 6-O-β-d-triglucoside (7). Structures of 1 and 2 were elucidated by NMR and HR-ESI-MS spectroscopic analysis. Their stereochemistry was determined by CD experiment. All compounds were tested for their ability to inhibit the formation of advanced glycation end-products in vitro. Compounds 1, 2, 3, 5, and 6 showed significant in vitro inhibitory activities (IC₅₀ values of 11.63, 23.40, 7.32, 89.03, and 38.89 µM, respectively).