Hypotensive effects on spontaneously hypertensive rats and antifungal activity on various species of Fusarium oxysporum of diethylstilbestrol-related compounds

The diethylstilbestrol-related compounds 3,3'-dihydroxy-alpha, beta-diethyldiphenylethane (I), diethylstilbestrol (II) and hexestrol (III) showed hypotensive effects on spontaneously hypertensive rats (SHR) and antifungal activities against all Fusarium oxysporum sp. tested. As previously reported, I had strong hypotensive action on normotensive rats at the dose of 10 mg/kg, while II and III showed weak hypotensive effects on these rats at the same dose. In this work, all three compounds also had hypotensive actions on SHR at the same dose. I showed the strongest hypotensive effect (-80.0 +/- 5.0 mmHg, 10 mg/kg, i.v.) on both SHR and normotensive rats. The three compounds also had antifungal activities against five kinds of Fusarium oxysporum sp. tested. Especially, II strongly inhibited the growth of Fusarium oxysporum f. sp. raphani IFO-9972 (minimum inhibitory concentration (MIC): 1.0 micrograms/ml).     

Chemical composition and in vitro antimicrobial activity of the essential oil of the flowers of Tridax procumbens

The essential oil of the flowers of Tridax procumbens L. was obtained by hydro-distillation and analyzed by gas chromatography equipped with a flame ionization detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC/MS). Twenty-six compounds were identified, which comprised 90.6% of the total constituents. The most abundant compound was (Z)-falcarinol (25.9%), followed by alpha-selinene (15.3%), limonene (8.3%) and zerumbone (4.3%). Antimicrobial activity was tested against six Gram-positive and eight Gram-negative bacteria, and three fungi. The oil was active against the tested Gram-positive bacteria at a concentration range of 0.14 +/- 0.03 - 0.57 +/- 0.05 mg/mL, while 0.67 +/- 0.12 - 4.58 +/- 0.41 mg/mL was effective against the studied Gram-negative bacteria. Remarkable antifungal activity was found against the tested fungi at a concentration range of 0.06 +/- 0.008 - 0.10 +/- 0.01 mg/mL.     

Phytogrowth-inhibitory and antimicrobial activities of 3,4'-dihydroxy-alpha,beta-diethylstilbene, the isomer of diethylstilbestrol

3,4'-Dihydroxy-alpha,beta-diethylstilbene (I), like diethylstilbestrol (II), showed phytogrowth-inhibitory and antimicrobial activities. First, compound I showed strong growth-inhibitory activity against the roots of two kinds of plants. The inhibitory activity of I was almost equal to that of sodium 2,4-dichlorophenoxyacetate used as a positive control. The phytogrowth-inhibitory activity of I was much higher than that of II. Next, unlike II, I had broad antifungal spectrum against phathogenic fungi. Compound I showed antifungal activity against six kinds of Fusarium oxysporum sp. This compound also had antibacterial activity against pathogenic and plant-pathogenic bacteria. These antibacterial activities of I were as high as those of II, the isomer of I. It should be emphasized that by shifting one of the phenolic hydroxyl groups of II to meta-position, phytogrowth-inhibitory activity was largely increased, while antimicrobial activity was unchanged.     

Inhibitory activity of dihydrosanguinarine and dihydrochelerythrine against phytopathogenic fungi

The antifungal activities of dihydrosanguinarine and dihydrochelerythrine, isolated from the leaves of Macleaya microcarpa, were evaluated on 12 plant pathogenic fungi; the two compounds exhibited the highest antifungal activity against Botrytis cinerea Pers. Among the 11 tested plant pathogenic fungi in vitro, the two compounds showed the highest antifungal activity against B. cinerea Pers, with 95.16% and 98.32% mycelial growth inhibition at 50 μg mL?1, respectively. In addition, the two compounds inhibited spore germination in vitro in a concentration-dependent manner. They also showed potent protective and curative effects against Erysiphe graminis and B. cinerea in vivo. This is the first report on the antifungal activity of dihydrosanguinarine and dihydrochelerythrine against pathogenic plant fungi.     

Antimicrobial and antioxidant activities of essential oils of Satureja thymbra growing wild in Libya

The composition of essential oil isolated from Satureja thymbra, growing wild in Libya, was analyzed by GC and GC-MS. The essential oil was characterized by γ-terpinene (39.23%), thymol (25.16%), p-cymene (7.17%) and carvacrol (4.18%) as the major constituents. Antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. It possessed strong antioxidant activity (IC50 = 0.0967 mg/mL). The essential oil was also screened for its antimicrobial activity against eight bacterial and eight fungal species, showing excellent antimicrobial activity against the microorganisms used, in particular against the fungi. The oil of S. thymbra showed bacteriostatic activity at 0.001-0.1 mg/mL and was bactericidal at 0.002-0.2 mg/mL; fungistatic effects at 0.001-0.025 mg/mL and fungicidal effects at 0.001-0.1 mg/mL. The main constituents thymol, carvacrol and γ-terpinene also showed strong antimicrobial activity. The commercial fungicide bifonazole showed much lower antifungal activity than the tested oil.     

In vitro hypoglycemic and antimicrobial activities of Senecio leucanthemifolius Poiret

This study reports on the alpha-amylase inhibitory and antimicrobial activities of Senecio leucanthemifolius Poiret. Extracts of S. leucanthemifolius were tested for their antimicrobial and antifungal activities against seven different pathogenic microorganisms using the microdilution technique. The ethyl acetate extract exhibited a strong antibiotic activity against Staphylococcus aureus with a MIC value of 31.25 microg mL(-1), while the n-hexane extract showed a significant activity against dermatophytic fungi. S. leucanthemifolius extracts were tested also for their potential hypoglycemic activity through the in vitro inhibition of alpha-amylase. The dichloromethane extract inhibited alpha-amylase with a value of 56.6% at 0.05 mg mL(-1) and the n-butanol extract showed a value of 89.2% at 1 mg mL(-1).     

Synthesis and pharmacological evaluation in mice of halogenated cannabidiol derivatives

Six halogenated derivatives of cannabidiol (CBD, 1) substituted on the aromatic ring at the 3' and/or 5' position, 3'-chloro- (2), 3',5'-dichloro- (3), 3'-bromo- (4), 3',5'-dibromo- (5), 3'-iodo- (6) and 3',5'-diiodo-CBD (7) were synthesized and their pharmacological effects of barbiturate-induced sleep prolongation, anticonvulsant effects and locomotor activity were evaluated by intravenous (i.v.) injection in mice. 2 (10 mg/kg, i.v., 69 +/- 10 min) significantly prolonged pentobarbital-induced sleeping time by 3.1-fold, compared to control (22 +/- 2 min), although other 1 derivatives used did not significantly affect the sleeping time. 2, 4 and 6 (10 mg/kg, i.v.) significantly prolonged hexobarbital-induced sleeping time by 2.0-, 2.0- and 2.3-fold, respectively, compared with control (52 +/- 5 min). On the other hand, 1 and all halogenated derivatives did not significantly prolong barbital-induced sleeping time. The monohalogenated derivatives, 2, 4 and 6 were able to prolong pentobarbital and hexobarbital-induced sleeping time, although the dihalogenated derivatives, 3, 5 and 7 did not exhibit a prolongation of the sleeping time. All halogenated derivatives of 1 except for brominated derivatives (2, 3, 6, 7) tended to prolong tonic seizure latency induced by pentylenetetrazol. 1 and its halogenated derivatives did not exhibit any prolongation of seizure latency induced by picrotoxin or strychnine. Maximal electroshock test demonstrated that 1 and 4 exhibited almost the same potency in their anticonvulsant effects, although other 1 derivatives 2, 3, 5, 6 and 7 did not show significant effect up to a dose of 63 mg/kg, i.v. The ED50 values (mg/kg, i.v.) of 1 and 4 were 38 and 44, respectively. 1 and 4 also showed anticonvulsant effect in minimal and maximal electroshock-threshold tests. 2, 4 and 6 tended to decrease the total distance (horizontal activity) and number of rearings (vertical activity) of mice, whereas 3, 5 and 7 tended to increase the number of rearings. However, the effects of all derivatives were not statistically significant from the control. 2 and 4 were the most potent derivatives on pharmacological activities among the synthetic cannabinoids examined in the present study. These results indicate that monohalogenation of 1 leads to some modification of the pharmacological profile of CBD.     

Antifungal activity of essential oil from Asteriscus graveolens against postharvest phytopathogenic fungi in apples

The essential oils of the aerial parts of Asteriscus graveolens have been studied using GC and GC-MS. Twenty-eight compounds were identified in the essential oil amounting to 94.9% of the total oil. The aerial part oils showed similar chromatographic profiles and were characterized by having a high content of oxygenated sesquiterpenes with 6-oxocyclonerolidol (66.7% +/- 5.5) and 6-hydroxycyclonerolidol (8.8% +/-1.2) as the major components. The antifungal effect of the essential oil from A. graveolens leaves was evaluated in vitro against three phytopathogenic fungi of apples (Alternaria sp., Penicillium expansum, and Rhizopus stolonifer). The results suggest that this essential oil has fungicidal properties towards Alternaria sp. from direct contact assay at 0.2% (v/v) and to P. expansum from vapor assay tests at 80 microL.     

New 2-aryliminoimidazolidines. II. Synthesis and antihypertensive activity of 2-(biphenylimino)-imidazolidines.

For improvement of the duration of action of FR35447 (I), 2-(biphenylimino)imidazolidines (III) were synthesized and their hypotensive activity was tested against conscious normotensive rats. 2-(4'-Fluoro-[1,1'-biphenyl]-2-ylimino)imidazolidine (IIIl) exhibited superior hypotensive potency and was comparable to clonidine (II) in its duration of action. The structure-activity relationships of III are also described.     

新型含二甲氧基甲基嘧啶基磺酰脲衍生物的合成及生物活性

将二甲氧基甲基引入到嘧啶环的4位, 设计并合成了15个结构新颖的磺酰脲类衍生物. 初步生物活性测试结果表明, 目标化合物具有较好的除草活性. 在75 g/ha的剂量下, 化合物6a和6g对油菜的芽前除草活性为100%, 与对照药单嘧磺隆和氯磺隆相当; 在50 mg/L的浓度下, 化合物6i和6o对3种病菌的离体抑制率都超过80%, 与对照药百菌清和多菌灵接近.     

Synthesis and fungicidal activity study of novel daphneolone analogs with 2,6-dimethylmorpholine

A series of novel daphneolone analogs was designed and synthesized on the basis of natural product 1,5-diphenyl-2-penten-1-one(I) from Stellera chamaejasme L. as lead compound, whereby 2,6-dimethylmorpholine moiety was introduced to replace 1-phenyl group. Their structures were confirmed by IR,1H NMR, and HRMS(ESI) or elemental analysis,13 C NMR for some representative compounds. The two isomers of target compounds were separated and identified by NOESY technique and chemical method.All of the synthesized compounds have been evaluated for anti-plant pathogenic fungi activities. The results showed that some compounds exhibited moderate to good antifungal activities against tested fungi at the concentration of 50 mg/L. Among them, compound 7d, with a 4-bromine-substituted phenyl group and cis-2,6-dimethylmorpholine moiety, displayed best activity with an EC50 of 23.87 mmol/L against Valsa mali, superior to lead compound I. In addition, preliminary structure–activity relationship analysis indicated that, between two isomers of target compounds, the antifungal activities of the isomer with cis-2,6-dimethylmorpholine were better than the trans-isomer.     

Chemical composition and antimicrobial activity of the essential oil of the leaves of Feronia elephantum (Rutaceae) from north west Karnataka

The essential oil of the leaves of Feronia elephantum Corr. was analyzed by gas chromatography and gas chromatography/mass spectrometry. The main constituents were beta-pinene (28.4%), Z-anethole (22.1%), methyl chavicol (12.0%) and E-anethole (8.1%), among thirty-three identified compounds, which represented 92.6% of the total oil. The antimicrobial activity was tested against five Gram-positive and eight Gram-negative bacteria, and four fungi. The oil was active against Micrococcus luteus (Gram-positive bacterium), Proteus mirabilis (Gram-negative bacterium), Penicillium chrysogenum and Aspergillus niger (fungi) with MIC values of 0.31 +/- 0.06, 0.52 +/- 0.10, 0.20 +/- 0.50 and 0.26 +/- 0.52 mg/mL, respectively.     

Synthesis and pharmacological activity of 4-(4'-(chlorophenyl)-4-hydroxypiperidine) derivatives

A new series of 4-(4'-chlorophenyl)-4-hydroxypiperidine derivatives (2-5), substituted at nitrogen, were synthesized and tested as potential analgesic compounds as well as evaluated for their effect on hypotensive activity. Results showed that all the derivatives exhibit significant analgesic activity in male Wistar rats at a dose of 50 mg/kg of body weight after intramuscular injection, when tested by thermal stimuli (tail flick test). Pethidine was used as reference drug. Compounds 2, 3 and 5 produced reduction in blood pressure in normotensive rat.     

Fumigant Antifungal Activity of Myrtaceae Essential Oils and Constituents from <em>Leptospermum petersonii</em> against Three <em>Aspergillus</em> Species

Commercial plant essential oils obtained from 11 Myrtaceae plant species were tested for their fumigant antifungal activity against Aspergillus ochraceus, A. flavus, and A. niger. Essential oils extracted from Leptospermum petersonii at air concentrations of 56 × 10^-3 mg/mL and 28 × 10^-3 mg/mL completely inhibited the growth of the three Aspergillus species. However, at an air concentration of 14 × 10^-3 mg/mL, inhibition rates of L. petersonii essential oils were reduced to 20.2% and 18.8% in the case of A. flavus and A. niger, respectively. The other Myrtaceae essential oils (56 × 10^-3 mg/mL) only weakly inhibited the fungi or had no detectable affect. Gas chromatography-mass spectrometry analysis identified 16 compounds in L. petersonii essential oil. The antifungal activity of the identified compounds was tested individually by using standard or synthesized compounds. Of these, neral and geranial inhibited growth by 100%, at an air concentration of 56 × 10^-3 mg/mL, whereas the activity of citronellol was somewhat lover (80%). The other compounds exhibited only moderate or weak antifungal activity. The antifungal activities of blends of constituents identified in L. petersonii oil indicated that neral and geranial were the major contributors to the fumigant and antifungal activities.     

Novel metal complexes of 3-acetylcoumarin-2-hydrazinobenzothiazole Schiff base: Design,structural characterizations,DNA binding,DFT calculations,molecular docking and biological studies

Five new Cu (II), Zn (II), Pd (II), Ru (III) and Ag(I) complexes, derived from the 3-acetylcoumarin-2-hydrazinobenzothiazole Schiff base (Hachbt), have been synthesized and characterized. The structures were established with the aid of elemental analyses (C, H, N), FT-IR, ¹H-NMR, ESR, UV–visible and ESI-mass spectra. The complexes were also investigated by magnetic susceptibility, thermal gravimetric analysis (TG-DTA) and cyclic voltammetry measurements. The results suggest that the Schiff base ligand behaves in two different ways: neutral mono/bidentate or mono-negative bi/tridentate. The calf thymus DNA (CT DNA) binding affinities of Hachbt and its complexes have been examined by UV–visible spectroscopy. The antifungal activity of the compounds was also screened against two fungal species of wood-decay basidiomycetes using the agar dilution method. Different complexes caused a reduction in the fungal colony diameters at a media concentration of 100 μg/ml. The best antifungal activity was observed for the Pd (II) and Ag(I) complexes with a 60% and 79% reduction, respectively. The effect of the complexes on the ability of the same fungi to decolorize poly-R dye on agar plates was also tested. All of the complexes showed an enhanced effect on the decolorization ability and the Cu (II) and Ru (III) complexes exhibited the strongest effect at a media concentration of 5 μg/ml. Theoretical studies were performed for all the complexes using the DFT/B3LYP/6–31 + g(d) basis set for calculations on the ligand atoms and LAN2DZ for the Pd (II) complex. The optimized geometries were found to be in a good agreement with the proposed structures. The molecular docking calculations show that the binding affinity of the Pd (II) complex is −309.170-309.2 kcal/mol, which suggests complexation with the DNA minor groove.     

Design,Syntheses and Biological Activities of Novel Sulfonylureas Containing an Oxime Ether Moiety

Since sulfonylurea is one of the most potent acetohydroxyacid synthase(AHAS) inhibitors, a series of novel sulfonylureas containing an oxime ether moiety was designed and synthesized and their chemical structures were determined by means of ¹H nuclear magnetic resonance(NMR), ¹³C NMR and high-resolution mass spectrometry(HRMS). In the herbicidal bioassay, several compounds showed moderate to good herbicidal activities against dicotyledons, but their activities against monocotyledons decreased. The in vitro antifungal activity was tested at a dosage of 50 mg/L. And the results show that compounds 7l, 7m and 7n exhibit promising antifungal activities against six common plant pathogenic fungi. Further investigations on molecular modification are in progress.     

Influence and role of metal ions in enzymatic catalysis with e.c. 1.2.3.2. xanthine oxidase Application to trace analysis

The effect of metal ions on the reductive half-reaction of xanthine oxidase (XOD) in the catalytic conversion of xanthine into uric acid has been studied spectrophotometrically in Tris-HCl buffer at pH 7.4, 37 +/- 0.1 degrees and ionic strength 0.04M. Some metal ions display inhibitor properties, the sequence of inhibiting efficiency being Ag(I) > Hg(II) > Cu(II) > Cr(VI) > V(V) > Au(III) > Tl(I) and for these the I(50) values were determined. Only Tl(I), V(V) and Cu(II) showed reversible inhibition and therefore for these the mechanisms were assessed [competitive for V(V) and Tl(I); uncompetitive for Cu(II)]. The conditional inhibition constants (K(i)) were also determined. The effect of EDTA for protection of the enzyme against metal inhibition, and for its reactivation after inhibition, was also investigated. Utilization of the linear relationship between relative enzyme activity and inhibitor concentration allowed sensitive and selective (though not specific) determination of Ag(I) and Hg(II) (10(-9)-10(-8)M), and of Cu(II) and Cr(VI) (10(-7)-10(-6)M), the maximum relative error being +/- 4%. For a few metal ions, e.g., Ag(I) and Cr(VI), in the presence of EDTA, a certain specificity is observed.     

Pharmacokinetic study of puerarin in rat serum by liquid chromatography tandem mass spectrometry

A highly sensitive and specific atmospheric pressure chemical ionization liquid chromatography-tandem mass spectrometry method was developed for serum pharmacokinetic studies of puerarin in rats. Chromatography was carried out on a reversed-phase Phenomenex Synergi 4 microm Fusion-RP80 column (150 x 2.0 mm i.d.) using a mobile phase consisting of acetonitrile-water (10:90, v/v) in 10 mm NH(4)OAc with a flow rate of 0.2 mL/min. Puerarin was analyzed in the multiple reaction monitoring mode with a precursor/product ion transition of m/z 415/267. The method was demonstrated to be specific and sensitive, and a linear response was observed over a range of 2-5000 ng/mL in rat serum. The validated method was successfully applied to the characterization of the pharmacokinetics of puerarin in rat serum after oral administration to spontaneously hypertensive rats. The blood concentration-time profile of puerarin showed a rapid initial increase, reaching a maximum and then declining within 1 h. Puerarin could not be detected after 24 h. The main pharmacokinetic parameters for puerarin after oral administration were as follows: C(max) (3.54 +/- 2.03 mg/L), T(max) (0.68 +/- 0.37 h), AUC(0-t) (7.29 +/- 3.79 mg h/L), AUC(0-infinity) (9.17 +/- 4.87 mg h/L), T(1/2) (1.7 +/- 0.6 h), CL/F (7.24 +/- 4.27 L/h/kg) and V/F (17.88 +/- 13.55 L/h/kg).     

Measurement and pharmacokinetic analysis of unbound cephaloridine in rat blood by on-line microdialysis and microbore liquid chromatography

A technique involving rapid sampling of cephaloridine in rat blood was achieved using a combination of microdialysis and sensitive microbore liquid chromatography. A microdialysis probe was inserted into the jugular vein/right atrium of a Sprague-Dawley rat. Then after a real-time collection of the analyte by microdialysis, the dialysate was automatically injected into a liquid chromatographic system via an on-line injector. Following a 2 h stabilization period after the surgical procedure, cephaloridine (20 mg/kg, i.v.) was then administered via the femoral vein. Isocratic elution of cephaloridine was carried out with a mobile phase containing methanol-20 mM monosodium phosphate (25:75, v/v, pH 5.5), and the flow rate of the mobile phase was 0.05 mL/min within 10 min. Intra- and inter-assay accuracy and precision of the assay were each less than 10%. The in vivo recovery of the cephaloridine from the microdialysate was 49.7 +/- 8.0% and 42.4 +/- 8.4% for 0.5 and 1 microg/mL standards (n = 6), respectively. Based on the pharmacokinetic analysis, the elimination half-life was 32.2 +/- 8.6 min by cephaloridine administration (20 mg/kg, i.v., n = 6).     

Determination of total arsenic in serum and packed cellsof patients with renal insufficiency

In order to investigate the arsenic level in serum and packed cells of patients with renal insufficiency, total arsenic (As) concentrations were determined with hydride generation atomic absorption spectrometry (HGAAS) in serum (S) and packed cells (PC) of 31 non-dialyzed patients. The accuracy of the method was tested by the analysis of arsenic in 3 certified reference materials. Patients showed a three-fold increase of arsenic concentrations in serum and a two-fold increase of arsenic in packed cells compared with controls. Patients (n=10) with higher serum creatinine (>2.0 mg/dL), urea (>0.70 g/L) and urinary protein (mean+/-SD: 1.12+/-0.82 g/L) showed higher arsenic concentrations (5.8+/-3.3 microg/L in serum and 18.0+/-16.7 microg/kg in packed cells) compared with those with lower creatinine (<1.6 mg/dL), urea (<0.6 g/L) and urinary protein (mean+/-SD: 0.27+/-0.82 g/L) (n=16, serum arsenic 1.2+/-1.2 microg/L, packed cells arsenic 2.6+/-1.9 microg/kg). The significant differences (both p < 0.001) in S and PC-arsenic levels of patients in group I and II implies a relationship between the arsenic level and the degree of chronic renal insufficiency.