Characterisation of Phosphate Solubilising Bacteria in Sandy Loam Soil Under Chickpea Cropping System

With the aim to explore the possible role of phosphate-solubilizing bacteria (PSB) in phosphorus (P) cycling in agricultural soils, we isolated PSB inhabiting naturally in the sandy loam soils under chickpea cropping of Patiala (Punjab State). A total of 31 bacterial isolates showing solubilizing activities were isolated on Pikovskaya agar plates. The potent phosphate solubilizers were selected for further characterization. These isolates were shown to belong to the genera Pseudomonas and Serratia by partial sequencing analysis of their respective 16S rDNA genes. ERIC-PCR based fingerprinting was done for tracking the survival of introduced populations of the PSB during mass inoculation of these strains under chickpea plots. The results showed positive correlation (r² = 0.853) among soil phosphatase activity and phosphate solubilizers population, which was also positively correlated (r² = 0.730) to available phosphorus. Identification and characterization of soil PSB for the effective plant growth-promotion broadens the spectrum of phosphate solubilizers available for field application.     

Rheological, water uptake and controlled release properties of a novel self-gelling aldehyde functionalized chitosan

In this work, aldehyde-functionalized chitosan was used to prepare gels through Schiff base formation between the aldehyde and the free amine groups. The gels, which were formed in situ without an external crosslinker, were characterized in respect to their rheological properties and water uptake capacity. In addition, the potential use of these gels as drug carriers was investigated using metronidazole (Mw 171Da), FTIC-dextran (Mw 40kDa) and bovine serum albumin (Mw 66kDa), as the model drugs. Higher concentrations of the aldehyde-functionalized chitosan originated more rigid gels, as evidenced by the higher values of complex modulus (G*). The highly porous structure of these gels allowed for more than 400% of water uptake. The release of the model drugs followed a near zero-order release profile. The molecular size as well as the pH of the medium influenced the amount of drug released, where the higher the pH, the slower the resulting drug release.     

Changes in the Weathering Activity and Populations of Culturable Rock-Weathering Bacteria from the Altered Purple Siltstone and the Adjacent Soil

A total of 150 bacteria were isolated from the less and more altered (weathered) purple siltstones and the adjacent soils to compare the changes in the rock weathering patterns and populations of rock-weathering bacteria. The proportions of the highly effective Fe and Si solubilizers were significantly different among the altered rocks and soils. Maximum proportions of the highly effective Fe, Si, and Al solubilizers were observed in the soils, while significantly higher proportion of the highly effective K solubilizers was observed in the more altered rocks and the soils. The rock-weathering bacteria belonged to 37 bacterial species, among which 36, 64, and 56% of the species were specific to the less and more altered rocks and the soils, respectively. In the rock-weathering process, strains M78 and L38 mainly produced acetic acid, while strain H28 mainly produced gluconic acid. Furthermore, dominant rock-weathering members of Ensifer genus had the higher ability to release Fe and Si, while dominant rock-weathering members of Bacillus had the higher ability to release K. The results suggest the changes in the element mobilization patterns and populations of the rock-weathering bacteria and highlight the possible role of these bacteria in the rock weathering and soil formation.     

Screening of non-alkaloidal natural compounds as acetylcholinesterase inhibitors

Acetylcholinesterase (AChE) inhibitors are currently the only approved therapy for the treatment of Alzheimer's disease, only a limited number of drugs are commercially available. A library of non-alkaloidal natural compounds was investigated. To this end, a convenient microtitre plate method for assaying AChE inhibition, which allows a complete kinetic analysis of AChE inhibitors, was developed. Seven active compounds with Ki values in the micromolar range were identified, six of which were xanthones. This is the first report that a promising potential for AChE inhibition exists in such non-nitrogenous natural compounds. Furthermore, four xanthones among these xanthones had already been described as monoamine oxidase (MAO) inhibitors, making then dual AChE/MAO inhibitors of great interest.     

Characterization of zinc-solubilizing Bacillus isolates and their potential to influence zinc assimilation in soybean seeds

One hundred thirty-four putative Bacillus isolates were recovered from soybean rhizosphere soils of Nimar region to select effective zinc solubilizers for increased assimilation of zinc (Zn) in soybean seeds. These isolates were screened in vitro for zinc-solubilization ability on Tris-minimal agar medium supplemented separately with 0.1% zinc in the form of zinc oxide, zinc phosphate, and zinc carbonate. Of all, 9 isolates and a reference Bacillus cereus ATCC 13061 were characterized and identified as Bacillus species based on Gram-positive reaction, endospore-forming cells, and the presence of iso-C??:? and anteiso-C??:? as predominant fatty acids. On plate assay, two isolates KHBD-6 and KHBAR-1 showed a greater diameter of solubilization halo and colony diameter on all the three zinc compounds. The isolates KHBD-6, KHBAR-1, BDSD-2-2C, and KHTH-4-1 and the reference strain ATCC 13061 had higher soluble zinc concentration in liquid medium supplemented with zinc phosphate and zinc carbonate compounds as compared with the other isolates and uninoculated control. Evaluation under microcosm conditions showed that inoculation of isolates KHBD-6 (57.34 μg/g), KHBAR-1 (55.67 μg/g), and strain ATCC 13061 (53.10 μg/g) significantly increased the Zn concentration in soybean seeds as compared with the other isolates and uninoculated control (47.14 μg/g). This study suggests the occurrence of zinc-solubilizing Bacillus in soils of Nimar region and isolates KHBD-6 and KHBAR-1 were found to be promising zinc solubilizers for increased assimilation of Zn in soybean seeds.     

Modulation of beta-amyloid metabolism by non-steroidal anti-inflammatory drugs in neuronal cell cultures

Alzheimer disease (AD) is characterized by cerebral deposits of beta-amyloid (Abeta) peptides, which are surrounded by neuroinflammatory cells. Epidemiological studies have shown that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD. In addition, biological data indicate that certain NSAIDs specifically lower Abeta42 levels in cultures of peripheral cells independently of cyclooxygenase (COX) activity and reduce cerebral Abeta levels in AD transgenic mice. Whether other NSAIDs, including COX-selective compounds, modulate Abeta levels in neuronal cells remains unexploited. Here, we investigated the effects of compounds from every chemical class of NSAIDs on Abeta40 and Abeta42 secretion using both Neuro-2a cells and rat primary cortical neurons. Among non-selective NSAIDs, flurbiprofen and sulindac sulfide concentration-dependently reduced the secretion not only of Abeta42 but also of Abeta40. Surprisingly, both COX-2 (celecoxib; sc-125) or COX-1 (sc-560) selective compounds significantly increased Abeta42 secretion, and either did not alter (sc-560; sc-125) or reduced (celecoxib) Abeta40 levels. The levels of betaAPP C-terminal fragments and Notch cleavage were not altered by any of the NSAIDs, indicating that gamma-secretase activity was not overall changed by these drugs. The present findings show that only a few non-selective NSAIDs possess Abeta-lowering properties and therefore have a profile potentially relevant to their clinical use in AD.     

Computer aided screening of inhibitors to 5-α reductase type 2 for prostate cancer

Traditionally, drugs are discovered by testing compounds synthesized in time consuming multi-step processes against a battery of invivo biological screens. Promising compounds are then further studied in development, where their pharmacokinetic properties, metabolism and potential toxicity were investigated. Here, we present a study on herbal lead compounds and their potential binding affinity to the effectors molecules of major disease like Prostate Cancer. Clinical studies demonstrate a positive correlation between the extent of 5-α reductase type 2 (isoform 2) and malignant progression of precancerous lesions in prostate. Therefore, identification of effective, well-tolerated 5-α reductase inhibitors represents a rational chemo preventive strategy. This study has investigated the effects of naturally occurring nonprotein compounds berberine and monocaffeyltartaric acid that inhibits 5-α reductase type 2. Our results reveal that these compounds use less energy to bind to 5-α reductase and inhibit its activity. Their high ligand binding affinity to 5-α reductase introduces the prospect for their use in chemopreventive applications. In addition, they are freely available natural compounds that can be safely used to prevent prostate cancer.     

Antiviral and cytotoxic activities of new derivatives of natural sesquiterpenes and taxol

Common occurrences of serious viral infections and a small number of available antiviral chemotherapeutics necessitate research for new, biologically active substances, which might be of use as antiviral drugs. Natural compounds, e.g., derived from plants and fungi, which show significant and various biological activities, may be a source of potential drugs. Sesquiterpenes, as well as taxol, and their derivatives, may serve as an example. The aim of the present study was to investigate the antiviral, antibacterial and cytotoxic properties of 7 new compounds: derivatives of sesquiterpenes of Lactarius mushroom origin and taxol--N-benzoylphenylisoserinates of sesquiterpenoid alcohols. The cytotoxicity of the tested compounds against Vero, RD, LLC-MK2 and A549 cell lines were assessed using the formazan method. All compounds showed a lower cytotoxicity than taxol. Their antiviral activity in vitro was evaluated by assessing the reduction of virus titre in cells subjected to the compounds in comparison to the cells, which were not subjected to them. It was found that out of 7 investigated compounds 3 exhibited antiviral activity. These compounds inhibited replication of HSV-1 virus in Vero cells. It appears therefore that further investigation of these groups of compounds and their derivatives is justified because they may constitute a potential source of chemotherapeutics.     

Inhibition of in vitro intracellular growth of Trypanosoma cruzi by dicationic compounds

Dicationic compounds, which are derivatives of pentamidine, are being developed for use as antiprotozoal drugs. These compounds bind to the minor groove of DNA and are thought to inhibit DNA-dependent enzymes and thereby prevent cellular replication by protozoans. The objective of this study was to test the ability of a group of these compounds to inhibit the intracellular and extracellular reproduction of Trypanosoma cruzi in vitro. At present, there are few drugs in use capable of inhibiting the intracellular stages of this parasite, and therefore compounds with this ability would be of value. Cultures of mouse fibroblasts were infected and treated with doses of dicationic compounds, and the numbers of parasites released at the end of the 5- to 7-day growth cycle were determined. Five of the compounds tested were found to be effective at inhibiting T. cruzi growth at doses that were not toxic to the host cells. The compound found most effective (DB709) inhibited parasite release at the low concentration of 0.8 ng/ ml, justifying further study. These results suggest that dicationic compounds may have potential as chemotherapy against T. cruzi infection.     

3D-QSAR study indicates an enhancing effect of membrane ions on psychiatric drugs targeting serotonin receptor 5-HT1A

Antidepressants and antipsychotics are psychiatric agents used for the treatment of various types of psychiatric diseases. Although currently among the most commonly prescribed drugs, their effectiveness and adverse effects are the topic of many studies and controversial claims. Here we generate QSAR models based on compounds series including 20 drugs recommended for two critical psychiatric diseases: depression and schizophrenia and we use these QSAR models to predict the biological activity of these 20 antidepressants and antipsychotics. We establish the membrane ions' contributions (sodium, potassium, calcium and iron) mediated by water to the antagonism of these drugs at the 5-HT1A receptor. The reliability of our QSAR models in predicting compounds activity is indicated by significant values for cross-validated correlation q2 (0.60-0.76) and fitted correlation r2 (0.96-0.98) coefficients. Our results indicate that potassium, calcium and iron play a key role for the antagonistic activity of drugs at the 5-HT1A receptor. Moreover, based on the established QSAR equations, we analysed 24 new escitalopram derivatives as possibly improved antidepressants targeting the 5-HT1A receptor. We identified that the presence of methyl groups and hydrogen atoms improves antidepressant activity while the simultaneous presence of ethyl, propyl or halogens decreased drastically antidepressant activity at the 5-HT1A site.     

QRAR models for cardiovascular system drugs using biopartitioning micellar chromatography

The capability of biopartitioning micellar chromatography (BMC) to describe and estimate pharmacological parameters of cardiovascular system drugs has been studied. The retention of cardiovascular system drugs was studied using different pH of Brij-35 as micellar mobile phase in modified C(18) stationary phase. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. An adequate correlation between the retention factors (log k) and the toxicity (LD(50)) of cardiovascular system drugs was obtained.     

Drugs affecting the synthesis of glycerides and phospholipids in rat liver. The effects of clofibrate, halofenate, fenfluramine, amphetamine, cinchocaine, chlorpromazine, demethylimipramine, mepyramine and some of their derivatives.

The effects on glycerolipid synthesis of a series of compounds including many drugs were investigated in cell-free preparations and slices of rat liver. p-Chlorobenzoate, p-chlorophenoxyisobutyrate, halofenate, D-amphetamine, adrenaline, procaine and N-[2-(4-chloro-3-sulphamoylbenzoyloxy)ethyl]norfenfluramine had little inhibitory effect on any of the systems investigated. Two amphiphilic anions, clofenapate and 2-(p-chlorophenyl)-2-(m-trifluoromethylphenoxy)acetate, both inhibited glycerol phosphate acyltransferase and diacylglycerol acyltransferase at approx. 1.6 and 0.7 mm respectively. Clofenapate (1 mm) also inhibited the incorporation of glycerol into lipids by rat liver slices without altering the relative proportions of the different lipids synthesized. The amphilic amines, mepyramine, fenfluramine, norfenfluramine, hydroxyethylnorfenfluramine, N-(2-benzoyloxyethyl)norfenfluramine, cinchocaine, chlorpromazine and demethylimipramine inhibited phosphatidate phosphohydrolase by 50% at concentrations between 0.2 and 0.9 mm. The last four compounds inhibited glycerol phosphate acyltransferase by 50% at concentrations between 1 and 2.6 mm. None of the amines examined appeared to be an effective inhibitor of diacylglycerol acyltransferase. Norfenfluramine, hydroxyethylnorfenfluramine and N-(2-benzoyloxyethyl)norfenfluramine produced less inhibition of glycerol incorporation into total lipids than was observed with equimolar clofenapate. The major effect of these amines in liver slices was to inhibit triacylglycerol and phosphatidylcholine synthesis and to produce a marked accumulation of phosphatidate. The results are discussed in terms of the control of glycerolipid synthesis. They partly explain the observed effects of the various drugs on lipid metabolism. The possible use of these compounds as biochemical tools with which to investigate the reactions of glycerolipid synthesis is considered.     

Skin permeability of various non-steroidal anti-inflammatory drugs in man

The skin permeabilities of a series of eight salicylates and ten non-steroidal anti-inflammatory drugs were investigated in human subjects. The logarithms of % absorption through intact skin and of n-octanol/water partition coefficients (log P) of the test compounds were plotted against one another, and a parabolic relationship was obtained in both compound series.     

Determination of three main antileprosy drugs and their main metabolites in serum by high-performance liquid chromatography

The simultaneous analysis of main antileprosy drugs such as 4,4′-diaminodiphenyl sulfone (DDS), clofazimine, rifampicin and their main metabolites in serum was examined by high-performance liquid chromatography using a μBondapak C_1a column. When the drugs dissoluted from serum were developed by tetrahydrofuran—0.5% acetic acid (40:60), clofazimine and rifampicins could be analyzed separately. Apart from the mutual separation of water-soluble conjugates of DDS, the individual analysis of DDS, its main liposoluble metabolite and a few related sulfone compounds is possible when the drugs are first developed by acetonitrile—water (20:80). By the use of tetrahydrofuran—water (50:50) containing PIC B-5, the rapid measurement of clofazimine isolated from the other compounds is also possible.     

The decomposition of benzodiazepines during analysis by capillary gas chromatography/mass spectrometry

A capillary gas chromatography column directly interfaced to a mass spectrometer was used for the analysis of sixteen benzodiazepines. The thermal stability of the drugs was found to be related to their chemical structure. Nine of the benzodiazepines were thermally unstable indicating that care should be taken in the interpretation of gas chromatographic data from this class of drugs. The unstable benzodiazepines were: ketazolam which decomposes to diazepam; N-4 oxides (chlordiazepoxide and demoxepam) which lose an oxygen radical; aromatic 7-nitro compounds (nitrazepam and clonazepam) which are partially reduced to the corresponding amine; alpha-hydroxy ketones (lorazepam and oxazepam) which decompose with the loss of water and N-methyl-alpha-hydroxy ketones (lormetazepam and temazepam) which partially decompose with the loss of a hydrogen molecule to produce the corresponding alpha, beta-diketones. Few problems were encountered in distinguishing the drugs by their mass spectra, the exceptions being ketazolam which decomposes to diazepam and demoxepam which decomposes to desmethyldiazepam. In general, good spectra were obtained from 20-50 ng of drug injected. However, for those compounds where the decompositions were not quantitative (nitrazepam, clonazepam, lormetazepam, temazepam) detection limits were poor.     

Species specific differences in the toxicity of mithramycin, chromomycin A3, and olivomycin towards cultured mammalian cells

Three structurally related anticancer drugs, mithramycin, chromomycin A3, and olivomycin, showed large unexpected differences (up to more than 1000 fold) in their toxicity towards cultured cells from various species (human, Chinese hamster, Syrian hamster, and mouse). Among the cell types examined, human cells (both a diploid fibroblast cell strain and HeLa cells) were maximally sensitive to all these drugs, followed by the Syrian hamster kidney cells (BHK 21). The mouse (LMTK- cells) and Chinese hamster (CHO) cells, which were more resistant, showed interesting differences in their sensitivity towards these drugs. For example, whereas the mouse cells were more resistant to mithramycin than CHO cells, the sensitivity pattern was reversed for both chromomycin A3 and olivomycin. In cell extracts derived from human, mouse, and Chinese hamster cells RNA synthesis, which is the cellular target of these drugs, showed identical sensitivity to both mithramycin and chromomycin A3, indicating that the species specific differences in the toxicity to these drugs are at the level of cellular entry of these compounds. Based on the structures of these glycosidic antibiotics and their patterns of toxicity, it is suggested that the intracellular transport of these drugs involves specific interactions between the sugar residues on these compounds and some type of cell surface receptor(s), which differ among different cell types. Some implications of these results for toxicity studies are discussed.     

Reactivity of nitro-thiophene derivatives with electron and oxygen radicals studied by pulse radiolysis and polarographic techniques

Summary A new series of nitrothiophene derivatives have been synthetized and some of the physico-chemical parameters which can influence both their radiosensitizing efficiency and toxicity have been investigated. These include octanol/water partition coefficient (P), one-electron reduction potential (E ₇ ¹ ) and reactivity of the drugs towards primary radical species. For these studies, pulse radiolysis techniques and conventional polarography have been extensively used. Biological responses (both sensitization and toxicity) have been tested towards Chinese Hamster cells in vitro. The results are valuable in selecting, among the tested compounds, 5-NTMA, 5-NTM, 4- and 5-NTCA as the nitrothiophenes promising for in vivo applications.     

Lipophilic phosphonium-lanthanide compounds with magnetic, luminescent, and tumor targeting properties

Multifunctional phosphonium-lanthanide compounds that simultaneously possess paramagnetism, luminescence, and tumor mitochondrial targeting properties were prepared by use of a facile method. These compounds were fully characterized by use of ¹H, ¹³C, ³¹P NMR, FT-IR, and elemental analyses. The thermal properties of these compounds including melting points and decomposition temperatures were investigated using DSC and TGA analyses. In addition, the paramagnetism, luminescence, and tumor targeting properties of these multifunctional compounds were confirmed by respective use of SQUID, fluorescence, and cell cytotoxicity studies. All compounds exhibited paramagnetism at room temperature, which could provide target delivery of these compounds to parts of the body containing tumor cells using a strong external magnetic field. In addition, these compounds display two major characteristic emissions originating from Dy^3 +, which can be utilized for imaging tumor cells. The IC₅₀ values of these compounds measured against normal breast cell line (Hs578Bst) are significantly greater than those measured against the corresponding carcinoma breast cell line (Hs578T), clearly indicating the selective tumor targeting properties of these compounds. Confocal fluorescence microscopy studies were used to confirm the yellowish-green fluorescence corresponding to the emission of dysprosium thiocyanate anion within cancer cells upon exposure of cancer cell lines such as human pancreatic carcinoma cell line (MIAPaCa-2) and human breast carcinoma (MDA-MB-231) to a solution of these phosphonium-dysprosium compounds.     

Bioremediation of polynitrated aromatic compounds: plants and microbes put up a fight

Industrialization and the quest for a more comfortable lifestyle have led to increasing amounts of pollution in the environment. To address this problem, several biotechnological applications aimed at removing this pollution have been investigated. Among these pollutants are xenobiotic compounds such as polynitroaromatic compounds--recalcitrant chemicals that are degraded slowly. Whereas 2,4,6-trinitrophenol (TNP) can be mineralized and converted into carbon dioxide, nitrite and water, 2,4,6-trinitrotoluene (TNT) is more recalcitrant--although several microbes can use it as a nitrogen source. The most effective in situ biotreatments for TNT are the use of bioslurry (which can be preceded by an abiotic step) and phytoremediation. Phytoremediation can be enhanced by using transgenic plants alone or together with microbes.     

Synthesis and antiproliferative activity of some steroidal lactone compounds

Using cholesterol as starting material, some steroidal lactone compounds with the structures of 3-substituted-6-oxo-7-oxa-B-homo-cholestane or 3-substituted-7-oxo-6-oxa-B-homo-cholestane were synthesized by oxidation, reduction, Baeyer-Villiger reaction and condensation reaction. The cytotoxicity of these compounds against MGC 7901 (human gastric carcinoma), HeLa (human cervical carcinoma) and SMMC 7404 (human liver carcinoma) cells was investigated. Our results showed that the synthesized compounds displayed a distinct cytotoxicity against these cancer cells. In particular, compounds 8 and 9 have similar cytotoxic capability as cisplatin does. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.