Optimal conditions for the production of sulfated polysaccharide by marine microalga Gyrodinium impudicum strain KG03

A marine microalga Gyrodinium impudicum strain KG03 produced sulfated exopolysaccharide designated as p-KG03, which showed a strong antiviral activity against encephalomyocarditis virus (EMCV). To optimize culture conditions for the production of p-KG03, mineral salts, vitamins, plant growth hormones, temperature, pH and light conditions were examined. From this study, M-KG03 medium for the maximum production of p-KG03 was suggested as follows; NH(4)Cl 75 microM, NaH(3)PO(4) 200 microM, NaHCO(3) 50 microM, Na(2)SO(4) 10 microM, FeCl(2) x 6H(2)O 10 microM, MnCl(2) x 4H(2)O 0.1 microM, vitamin B(12) 0.75 microg, naphthalene acetic acid (NAA) 7.5 microg and myo-inositol 200 mg per liter of aged sea water. The optimal temperature and pH were 22.5 degrees C and 8.0, respectively. The optimal light conditions of intensity and period were 150 microE m(-2) s(-1) and 16:8 h light:dark cycle. Finally, the cell growth and p-KG03 production were measured in one liter of M-KG03 medium with 1% CO(2) and 50 ml min(-1) of airflow using two liters airlift balloon type photobioreactor (ABTPR). At these optimal conditions, p-KG03 production and cell growth were 134.6+/-5.9 mg l(-1) and 123,076+/-1,597 cells ml(-1), respectively, representing a 7.7 and 5.1 times compared with f/2 medium with Erlenmeyer flask culture (p-KG03 production 17.5+/-1.3 mg l(-1) and cell growth 24,311+/-1,291 cells ml(-1)).     

Isolation of four aquatic streptomycetes strains capable of growth on organochlorine pesticides

Ninety-three wild-type isolates identified as actinomycetes were tested against 11 organochlorine pesticides (OPs): aldrin, chlordane, DDD, DDE, DDT, dieldrin, heptachlor, and heptachlor epoxides, lindane, and methoxychlor. Qualitative screening agar assays displayed 62-78% tolerance of strains to OPs. Four strains designed M4, M7, M9 and M15 were selected based on multi-OP-tolerance, and identified as members of the streptomycetes group. Different growth profiles were observed in cultures of the four selected streptomycetes cultured in synthetic medium containing 5-50 microg x l(-1) aldrin or chlordane or lindane. Increase of aldrin removal by the selected microorganisms was concomitant with the 4.8-36.0 microg x l(-1) pesticide concentration range. After 72 h of streptomycete M7 growth in synthetic medium containing 48.0 microg x l(-1) aldrin, the remaining OP concentration in the supernatant was approximately 10% of the initial concentration. Also, in stationary growth phase less than 2.5 microg x l(-1) aldrin residual concentration was detected in the medium.     

Microcystin-LR, a cyanobacterial toxin, induces growth inhibition and histological alterations in common reed (Phragmites australis) plants regenerated from embryogenic calli

The aim of this study was to establish the histological effects of exposure to microcystin-LR (MC-LR), a cyanotoxin, on axenic Phragmites australis plantlets. Plantlets were regenerated from embryogenic reed calli by tissue culture methods. Microcystin-LR inhibited the growth and development of embryogenic calli and the growth of reed plantlets. The 50% plantlet growth inhibitory concentration value (IC50) of MC-LR was 12 microg ml(-1) (12.07 microM) on mineral medium and 36 microg ml(-1) (36.22 microM) on Murashige-Skoog medium. In the case of roots, the IC50 value was 4.1 microg ml(-1) (4.12 microM) on both media. Microcystin-LR induced aerenchyma obturation, altered lignification of cell walls in the axial organs, root necrosis and the capture of lateral or adventitious roots in the tissues of axial organs of reed plantlets. Cyanotoxin induced the premature development of lateral roots, root coalescence and early aerenchyma formation. Our data suggest that microcystin-LR, a cyanotoxin, induced developmental and histological alterations leading to growth inhibition of reed, and the induced harms have an impact on understanding reed decay in eutrophic fresh waters.     

Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues.

Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinolone (BSTFA 1% TMCS) followed by equimolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-l were obtained in 40-77% yields. The esters 2a-j and 2l were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 microM, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7+/-0.04 and 0.8+/-0.09 microM, respectively. Both compounds were not toxic towards the Vero cell line.     

Prostaglandin-H-synthase (PGHS)-1 and -2 microtiter assays for the testing of herbal drugs and in vitro inhibition of PGHS-isoenzyms by polyunsaturated fatty acids from Platycodi radix

In order to test inhibition of prostaglandin-H-synthase-1 and -2 (PGHS-1 and -2) by plant extracts, we have established two enzyme based in vitro assays with enzyme immunoassay (EIA) evaluation. The assays have been evaluated with known synthetic inhibitors and with plant extracts. In a screening of traditionally used Chinese herbs for anti-inflammatory activity, a series of n-hexane and dichloromethane extracts showed significant inhibitory effect in comparison with the known specific PGHS-2 inhibitors NS-398 (IC(50) = 2.6 microM) and nimesulide (IC(50) = 36 microM). The lipophilic extracts of the Chinese drug Jiengeng, the dried roots of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae), showed good inhibitory activity against both PGHS isoenzymes. The directly prepared DCM-extract exhibited better activity against PGHS-2 (IC(50) = 4.0 microg/ml) than against PGHS-1 (IC(50) = 17.6 microg/ml). We identified fatty acids as main active constituents and quantified them. Linoleic acid showed the highest content (ca. 20% of the dried extract) and a high and preferential PGHS-2 inhibitory activity (IC(50) (PGHS-1) = 20 microM; IC(50) (PGHS-2) = 2 microM). The comparison of the concentration of linoleic acid and the inhibitory activity of the direct DCM-extract showed, that linoleic acid is mainly responsible for the in vitro activity of the extract on PGHS-2.     

Mytilus trossulus hsp70 as a biomarker for arsenic exposure in the marine environment: laboratory and real-world results.

The highly conserved heat shock protein 70 (hsp70) is induced by heat and chemical toxins, particularly heavy metals such as arsenic (As). The use of Mytilus trossulus (bay mussel) hsp70 as a 'screening' biomarker for marine heavy metals contamination was assessed. Some studies have found high hsp70 sensitivity to heavy metals, while others have found the opposite. Few studies have realistically used low heavy metals exposures, and fewer have used real-world contamination exposures. Clean sub-tidal mussels from the Puget Sound, Washington State (WA), USA, were acclimatized for 2 weeks and exposed for 24 h to As-spiked seawater (n=9) or to contaminated seawater from an arsenical pesticide plant in Tacoma, WA (n=10) followed by a Western blot for hsp70. Hsp70 inductions were insignificant at 10 microg l(-1) As(III), but were strong at 100 microg l(-1) (p<0.05) and 1000 microg l(-1) (p<0.01), with the induction threshold estimated at 30-50 microg l(-1) As(III). Hsp70 induction roughly correlated with arsenical toxicity, with As(III) > As(V) > (CH(3))(2)As(V). Altogether, the inter-individual variability of hsp70 levels tends to mask inductions at low As concentrations, making it a crude toxicity biomarker. In addressing this problem, the following options could prove promising: (1) pre- or post-stressing specimens for greater hsp70 sensitivity, (2) use of internal protein controls such as actin, (3) use of hsp70-reporter gene constructs, and (4) detection with hsp60, heme oxygenase-1, metallothionein, CYP450, MXR or GPx.     

Endothelium-dependent hypotensive and vasorelaxant effects of the essential oil from aerial parts of Mentha x villosa in rats.

Cardiovascular effects of an essential oil from the aerial parts of Mentha x villosa (OEMV) were tested in rats using a combined in vivo and in vitro approach. In non-anesthetized normotensive rats, OEMV (1, 5, 10, 20, 30 mg kg(-1) body wt., i.v.) induced a significant and dose-dependent hypotension (-3 +/- 1.8%; -6 +/- 0.7%; -40 +/- 6.7%; -58 +/- 3.8%; -57 +/- 2.1%, respectively) associated with decreases in heart rate (-1 +/- 0.3%; -9 +/- 0.9%; -17 +/- 3.2%; -72 +/- 3.1%; -82 +/- 1.4%, respectively). The hypotensive and bradycardic responses evoked by OEMV were attenuated and blocke by pre-treatment of the animals with atropine (2 mg kg(-1) body wt., i.v.). In isolated rat atrial preparations, OEMV (10, 100, 300, 500 microg ml(-1)) produced concentration-related negative chronotropic and inotropic effects (IC50 value = 229 +/- 17 and 120 +/- 13 microg ml(-1), respectively). In isolated rat aortic rings, increasing concentrations of OEM (10, 100, 300, 500 microg ml(-1)) were able to antagonize the effects of phenylephrine (1 microM), prostaglandin F2alpha (10 microM) and KCl (80 mM)-induced contractions (IC50 value = 255 +/- 9, 174 +/- 4 and 165 +/- 14 microg ml(-1), respectively). The vasorelaxant activity induced by OEMV was attenuated significantly by either endothelium removal (IC50 value = 304 +/- 9 microg ml(-1)), NG-nitro L-arginine methyl ester (L-NAME) 100 microM (IC50 value=359 +/- 18 microg ml(-1)), L-NAME 300 microM (IC50 value = 488 +/- 20 microg ml(-1)) or indomethacin 10 microM (IC50 value = 334 +/- 18 microg ml(-1)). However, it was not affected by atropine 1 microM (IC50 value = 247 +/- 12 microg ml(-1)). Furthermore, the hypotensive response induced by OEMV was attenuated significantly after nitric oxide (NO) synthase blockade (L-NAME, 20 mg kg(-1) body wt., i.v.), while bradycardia was not altered. The results suggest that the hypotensive effect induced by OEMV is probably due to its direct cardiodepressant action and peripheral vasodilation, which can be attributed to both endothelium-dependent (via EDRFs, at least NO and prostacyclin) and endothelium-independent mechanisms (such as Ca2+ channel blockade).     

Synthesis and biological evaluation of some new N(4)-substituted isatin-3-thiosemicarbazones

A new series of 12 N(4)-substituted isatin-3-thiosemicarbazones 2a-l has been synthesized, characterized and screened for in vitro cytotoxic, phytotoxic and urease inhibitory effects. All the compounds proved to be active in the brine shrimp bioassay; 2a, 2b, 2d, 2f and 2h-l exhibited a high degree of cytotoxic activity (LD(50) = 1.10 x 10(- 5) M-3.10 x 10(- 5) M). In urease-inhibition assay, compounds 2a, 2b, 2e, 2f, 2h-j and 2l proved to be potent inhibitors displaying relatively much greater inhibition of the enzyme with IC(50) values ranging from 20.6 microM to 50.6 microM. Amongst these, 2a and 2f were found to be the most potent ones exhibiting pronounced inhibition with IC(50) value 20.6 microM. All the synthetic compounds showed weak to moderate (10-40%) phytotoxicity at the highest tested concentration (500 microg/mL) indicating their usefulness as inhibitors of soil ureases.     

Arylfurans as potential trypanosoma cruzi trypanothione reductase inhibitors

The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC50 of 48.5 microM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60% at 20 microg/ml (59 and 90 microM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 microg/ml (0.6-1.5 mM).     

Discovery of substituted 4-anilino-2-(2-pyridyl)pyrimidines as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. Part 1: structure-activity relationships of the 4-anilino group

A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS assay. Compound 5a was found to arrest T47D cells in G2/M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta-position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (5a) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (5l), was obtained through the SAR studies. Compound 5l is highly active with an EC50 value of 18 nM in the caspase activation assay in T47D breast cells. Interestingly, 5a and other meta-mono-substituted compounds were active against T47D cells but were not active against H1299 and HT29 cells, while 5l and other 2,5-disubstituted compounds were active against all the three cells. In a tubulin polymerization assay, compound 5l inhibited tubulin polymerization with an IC50 value of < 0.5 microM, while 5a was not active up to 50 microM.     

Development of a scintillation proximity assay for beta-ketoacyl-acyl carrier protein synthase III

Assays of beta-ketoacyl-acyl carrier protein synthases III (KASIII; FabH), a key enzyme initiating bacterial type II fatty acid biosynthesis, usually involve incubation of radiolabeled acetyl-coenzyme A and malonyl-acyl carrier protein (MACP). The radiolabeled acetoacetyl-ACP product is precipitated and separated from the substrate before quantitation. We have developed a scintillation proximity assay (SPA) where use of biotinylated MACP (BMACP) allows the generation of a biotinylated acetoacetyl-ACP. This product, when captured by the streptavidin-coated scintillant-impregnated microspheres, generates an SPA signal. A BMACP K(m) of 7.1 microM was determined using this SPA with the Streptomyces glaucescens FabH. A similar MACP K(m) (6 microM) was determined in a precipitation assay, demonstrating that BMACP is an effective substrate for FabH. IC(50) values of 15.2 microM (SPA) and 24.8 microM were obtained with iodoacetamide and the S. glaucescens FabH. Comparable IC(50) values of 160 microM (SPA) and 125 microM were also obtained with the antibiotic thiolactomycin and the Escherichia coli FabH. These observations demonstrate that FabH inhibitors can be readily detected using a SPA with BMACP and that the effectiveness of inhibitors in the SPA is comparable to that obtained using MACP and a standard TCA precipitation assay. A FabH SPA adaptable to high-throughput screening should facilitate the discovery of potential novel antibiotics.     

Serotonergic and dopaminergic influence of the duration of embryogenesis and intracapsular locomotion of Lymnaea stagnalis L

The role of the dopaminergic and serotonergic system was studied during the embryonic development of the pond snail Lymnaea stagnalis, with special attention to the effect of dopamine and serotonin as well as their agonists and antagonists on the rotation of the veliger larvae, and to the effect of precursors and inhibitors of the synthetizing enzymes on the duration of the embryonic life. Serotonin, D-lysergic acid diethylamide and N,N-dimethyltryptamine increased at a concentration of 1 microM the rotation by 50%, 90% and 87% respectively, and among them D-Lysergic acid diethylamide was found to be the most potent agonist. Other serotonergic agonists and antagonists enhanced the frequency of the rotation (from 165% to 355%) at higher threshold concentrations in the following rank order: methysergid > tryptamine > 2,5-dimethoxy-4-iodoamphetamine > 5-carboxyamidotryptamine > bromo-lysergic acid diethylamide > 7-methyltryptamine. Application of 1-(2-methoxyphenyl) piperazine decreased the rotation by 76%. The reuptake inhibitor desipramine completely blocked the rotation and killed the embryos. Dopaminergic agonists accelerated the rotation by 62% to 233%, and their effect was ranged as follows: dopamine > apomorphine > m-tyramine approximately equal to p-tyramine. Chlorpromazine at 100 microM concentration killed the embryos. At a concentration of 100 microg/ml, tyrosine, the precursor of DA, slowed down the embryonic development by increasing the duration of the embryonic life from 8 to 10 days. Decarboxylase inhibitors, alpha-methyl-3,4-dihydroxyphenyl-alanine (25 microg/ml) and m-hydroxybenzylhydrazin (5 microg/ml), killed 50% of the embryos, meanwhile the rest hatched ten days later, compared to the control animals. The development was partially blocked by the serotonin precusor L-tryptophane (50 microg/ml). Trytophan hydroxylase blocker, p-chlorphenylalanine (50 microg/ml) resulted in a distortion of the body pattern of the embryos, and prevented the hatching of most (95%) of the animals.     

Spasmolytic action of the methanol extract and isojuripidine from Solanum asterophorum Mart. (Solanaceae) leaves in guinea-pig ileum

Solanum asterophorum Mart. (Solanaceae) is a shrub popularly known as "jurubeba-defogo" in the northeast of Brazil. In the present work, the methanol extract (SA-MeOH, 3750 microg/mL) and isojuripidine (10(-7) - 3 x 10(-4) M), a steroidal alkaloid obtained from S. asterophorum Mart. leaves, inhibited phasic contractions induced by both 1 microM histamine [IC50 = (225.8 +/- 47.4), g/mL and (3.5 +/- 0.8) x 10(-5) M] or 1 microm acetylcholine [IC50 = (112.5 +/- 20.6) microg/mL and (2.3 +/- 0.4) x 10(-5) M] in guinea-pig ileum, respectively. The extract and isojuripidine also relaxed the ileum (SA-MeOH, 1-750 microg/mL, and isojuripidine, 10(-9) - 3 x 10(-4) M) pre-contracted with 1 M histamine [EC50 = (101.1 +/- 17.4) microg/mL and (1.2 +/- 0.3) x 10(-6) M] or 1 microM acetylcholine [EC50 = (136.8 +/- 21.1) microg/mL and (1.9 +/- 0.4) x 10(-6) M] or 40 mm KCl [EC50 = (149.4 +/- 19.5) microg/mL and (1.8 +/- 0.7) x 10(-6) M], respectively, in an equipotent and concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-operated calcium (Ca(v)) channels. To confirm this hypothesis, we evaluated their effect on cumulative CaCl2 curves in depolarizing medium nominally without Ca2+. SA-MeOH (27, 243, 500, and 750 microg/mL) and isojuripidine (3 x 10(-8), 10(-6), 3 x 10(-5), and 3 x 10(-4) M) inhibited the contractions induced by CaCl2, in a concentration-dependent manner. The concentration-response curves to CaCl2, in the presence of SA-MeOH and isojuripidine, were shifted downward in relation to a control curve in a non-parallel manner resulting in reduction of the maximum effect [E(max) = (71.2 +/- 9.2); (57.4 +/- 9.2); (43.8 +/- 3.4); (41.5 +/- 2.4) and (90.6 +/- 4.8); (74.7 +/- 8.7); (66.4 +/- 3.9); (31.3 +/- 4.1)%, respectively]. SA-MeOH and isojuripidine present spasmolytic action in guinea-pig ileum due to a partially blockade of calcium influx through Ca(v) channels.     

Antioxidant and radioprotective effect of the active fraction of Pilea microphylla (L.) ethanolic extract

The ethanolic extract of Pilea microphylla (L.) was defatted, successively fractionated with acetone and the residue so obtained was found to be most potent when subjected to detailed free radical scavenging and in vivo radioprotection studies. The most active fraction reacts with free radicals, such as DPPH (50 microM), ABTS(.)(-) (100 microM) and (.)OH (generated by Fenton reaction) with IC(50) value of 23.15 microg/ml, 3.0 microg/ml and 310 microg/ml, respectively. The most active fraction inhibited iron-induced lipid peroxidation in phosphatidyl choline liposomes with an IC(50) of 13.74 microg/ml. The kinetics of scavenging of DPPH and ABTS(.)(-) radicals were followed at different concentrations of the fraction by employing stopped-flow studies. The observed first order decay rate constants at 200 microg/ml and 50 microg/ml of fraction with DPPH (50 microM) and ABTS(.)(-) (50 microM) were found to be 0.4s(-1) and 2.1s(-1), respectively. The fraction when screened for in vivo radioprotection in Swiss albino mice showed 80% protection at a dose of 900 mg/kg and with a DRF of about 1.12. The fraction was also found to protect livers of irradiated mice from depletion of endogenous antioxidant enzymes like glutathione, GST, SOD, catalase and thiols. The fraction also protected the villi height, increased the number of crypt cells while offering general protection to the intestine from acute radiation effects. The fraction also protected the hematopoietic system as assessed by endogenous spleen colony assay, contributing to the overall radioprotective ability.     

Isolation and characterization of a mannoglucan from edible Cordyceps sinensis mycelium

Cordyceps sinensis is a well known tonic food or invigorant with broad-spectrum medicinal properties that is widely used in the People's Republic of China. A neutral mannoglucan 1 with a molar mass of approximately 7.7x10(3) Da was obtained from the 0.05 M acetate buffer extract of C. sinensis mycelium. It had [alpha](D)(20)+126 (c 0.2, H(2)O) and consisted of Man and Glc units in the molar ratio of 1:9. A combination of chemical analysis and NMR and IR spectroscopy together with digestion with alpha-D-amylase showed 1 to have a alpha-D-glucan backbone with (1-->4)- and (1-->3)-linkages, and the side chains of alpha-D-(1-->6)-Manp were attached to the backbone via O-6 of alpha-(1-->3)-Glcp residues. Compound 1 showed weak cytotoxicity activity against SPC-I (IC(50)=63 microg/mL) cancer line, and no obvious cytotoxicity activities against BCAP37 (IC(50)>100 microg/mL) and SW480 (IC(50)>100 microg/mL) cancer lines.     

New biscoumarin derivatives-cytotoxicity and enzyme inhibitory activities

Biscoumarin derivatives 1-27 were tested for their inhibition of snake venom and human nucleotide pyrophosphatase phosphodiesterase-1 enzymes. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both the enzymes. Ki and IC50 values of biscoumarins were found to be in the range of 50 to 1000 and 164 to > 1000 microM, respectively, against human recombinant phosphodiesterase 1 enzyme and 8.0 to 1150 and 9.44 to > 1000 microM, respectively, against snake venom phosphodiesterase. Compounds 1, 3, 4, 6, 7, 17, 26, and 30 were found to be non-competitive and non-cytotoxic upto a concentration of 200 microg/mL as evident by less than 10% cell death after 3 h of incubation.     

Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin

Leptin is a polypeptide, mainly produced in white adipose tissue, and increases sympathetic nerve activity. A few studies investigated leptin's effect on peripheral vessels. We examined the vasorelaxant effects of human leptin on rat arteries. Arterial rings were precontracted with 1 x 10(-6) mol/l of phenylephrine, and leptin was superfused. Leptin relaxed phenylephrine-precontracted arterial rings in a dose-dependent manner. ED50 was calculated to 8.4 microg/ml. Removal of endothelium abolished the effects of leptin. Indomethacin (1 x 10(-5) mol/l) did not affect the vasorelaxation by leptin, whereas 1 x 10(-4) mol/l of N(omega)-nitro-L-arginine methyl ester (L-NAME) completely suppressed it. The inhibition was antagonized by 1 x 10(-4) mol/l of L-arginine. Leptin normally relaxed arterial rings during superfusion of K channel blockers, including 3 x 10(-5) mol/l of glibenclamide, 1 x 10(-6) of mol/l apamin, and 5 x 10(-7) mol/l of charybdotoxin. Low Cl(-) solution (8. 3 mmol/l) inhibited leptin-induced relaxation, but endothelium-independent vasodilatation by nitroprusside was not impaired at low Cl(-) solution. These results suggest that arterial relaxation by leptin is mediated by nitric oxide released from endothelium, and Cl(-) plays an important role in leptin-induced nitric oxide release.     

Newer tetracycline derivatives: synthesis, anti-HIV, antimycobacterial activities and inhibition of HIV-1 integrase

A series of new tetracycline derivatives has been synthesized by reacting appropriate tetracyclines, formaldehyde and secondary amino (piperazino) function of fluoroquinolones using microwave irradiation with the yield ranging from 41 evaluated for its anti-HIV, antimycobacterial activities and HIV-1 integrase (IN) enzyme inhibition studies. Among the synthesized compounds, compound 10 was found to be the most promising compound active against HIV-1 replication with EC(50) of 5.2 microM and was nontoxic to the CEM cells until 200 microM, and MIC of 0.2 microg/mL against Mycobacterium tuberculosis, with moderate inhibition of both 3'-processing and strand transfer steps of HIV-1 IN.     

A novel metal-chelating inhibitor of protein farnesyltransferase

A novel metal chelator comprising a 4-(naphthalen-1-yl)pyridine and 2-aminoethanethiol was synthesized. This showed inhibitory activity against human protein farnesyltransferase with IC(50) 1.9 microM, induced morphological change in K-ras-NRK cells at 0.5 microg/mL and showed growth inhibition of K-ras-NRK cells with IC(50) 0.32 microg/mL.