Products active on mosquitoes,IV: Synthesis and biological activity of 8-propargyloxy-3,7-dimethyl-2,6-octadienyl/6-octenyl ethers

Summary A series of 8-proparglyoxy-3,7-dimethyl-2,6-octadienyl and 8-propargyloxy-3,7-dimethyl-6-octenyl ethers were prepared from 8-hydroxygeranyl and 8-hydroxycitronellyl ethers, respectively. Almost all compounds showed high toxicity toCulex quinquefaciatus larvae at 1 mgl^–1 dose level.

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Gegen Mücken aktive Produkte, 4. Mitt.: Synthese und biologische Aktivität von 8-Propargyloxy-3,7-dimethyl-2,6-octadienyl/6-octenyl-ethern

Zusammenfassung Eine Reihe von 8-Propargyloxy-3,7-dimethyl-2,6-octadienyl- und 8-propargyloxy-3,7-dimethyl-6-octenyl-ethern wurden aus 8-Hydroxygeranyl- bzw. 8-Hydroxycitronellyl-ethern hergestellt. Fast alle Verbindungen zeigten hoch Toxizität gegenüber Larven vonCulex quinquefaciatus in einer Dosierung von 1 mgl^–1.

     

Chemometric data analysis of pollutants in wastewater—a case study

In this study, chemometric techniques such as cluster analysis (CA), discriminant analysis (DA), principal component analysis (PCA) and partial least squares (PLS) were used to analyse the wastewater dataset to identify the factors which affect the composition of sewage of domestic origin, spatial and temporal variations, similarity/dissimilarity among the wastewater characteristics of cis- and trans-drains and discriminating variables. Samples collected from 24 wastewater drains in Lucknow city and from three sites on Gomti river in the month of January/February, May, August and November during the period of 5 years (1994-1999) were characterized for 32 parameters. The multivariate techniques successfully described the similarities/dissimilarities among the sewage drains on the basis of their wastewater characteristics and sources signifying the effect of routine domestic/commercial activities in respective drainage areas. Spatial and seasonal variations in wastewater composition were also determined successfully. CA generated six groups of drains on the basis of similar wastewater characteristic. PCA provided information on seasonal influence and compositional differences in sewage generated by domestic and industrial waste dominated drains and showed that drains influenced by mixed industrial effluents have high organic pollution load. DA rendered six variables (TDS, alkalinity, F, TKN, Cd and Cr) discriminating between cis- and trans-drains. PLS-DA showed dominance of Cd, Cr, NO₃, PO₄ and F in cis-drains wastewater. The results suggest that biological-process based STPs could treat wastewater both from the cis- as well as trans-drains, however, prior removal of toxic metals will be required from the cis-drains sewage. Further, seasonal variations in wastewater composition and pollution load could be the guiding factor for determining the STPs design parameters. The information generated would be useful in selection of process type and in designing of the proposed sewage treatment plants (STPs) for safe disposal of wastewater.     

Chemometric analysis of groundwater quality data of alluvial aquifer of Gangetic plain, North India

Water quality data set from the alluvial region in the Gangetic plain in northern India, which is known for high fluoride levels in soil and groundwater, has been analysed by chemometric techniques, such as principal component analysis (PCA), discriminant analysis (DA) and partial least squares (PLS) in order to investigate the compositional differences between surface and groundwater samples, spatial variations in groundwater composition and influence of natural and anthropogenic factors. Trilinear plots of major ions showed that the groundwater in this region is mainly of Na/K-bicarbonate type. PCA performed on complete data matrix yielded six significant PCs explaining 65% of the data variance. Although, PCA rendered considerable data reduction, it could not clearly group and distinguish the sample types (dug well, hand-pump and surface water). However, a visible differentiation between the water samples pertaining to two watersheds (Khar and Loni) was obtained. DA identified six discriminating variables between surface and groundwater and also between different types of samples (dug well, hand pump and surface water). Distinct grouping of the surface and groundwater samples was achieved using the PLS technique. It further showed that the groundwater samples are dominated by variables having origin both in natural and anthropogenic sources in the region, whereas, variables of industrial origin dominate the surface water samples. It also suggested that the groundwater sources are contaminated with various industrial contaminants in the region.     

High-Performance Thin-Layer Chromatographic Determination of Satranidazole in its Dosage Form

JPC – Journal of Planar Chromatography – Modern TLC - A high-performance thin-layer chromatographic method has been developed for determination of a new antiamoebic drug, satranidazole,...     

Efficient and environmentally benign synthetic protocol for the synthesis of structurally diverse annulated pyridopyrimidines

Structurally diverse annulated pyridopyrimidines have been synthesized by an efficient and environmentally benign synthetic protocol involving catalyzed four-component reaction of 2-aminobenzothiazoles with thiophene-2-carbaldehyde and carbonyl compounds in ethanol. Mild reaction conditions, operational simplicity, and structural diversity with excellent yields are some special attractions of the present protocol.     

Oxidation of Antitubercular Drug Isoniazid by a Lipopathic Oxidant,Cetyltrimethylammonium Dichromate: A Mechanistic Study

The oxidation of an antitubercular drug isoniazid by a lipopathic oxidant cetyltrimethylammonium dichromate (CTADC) in a nonpolar medium generates isonicotinic acid both in the presence and the absence of acetic acid. The conventional UV–vis spectrophotometric method is used to study the reaction kinetics. The occurrence of the Michaelis–Menten–type kinetics with respect to isoniazid confirms the binding of oxidant and substrate to form a complex before the rate‐determining step. The existence of the inverse solvent kinetic isotope effect, k(H₂O)/ k(D₂O) = 0.7, in an acid‐catalyzed reaction proposes a multistep reaction mechanism. A decrease in the rate constant with an increase in [CTADC] reveals the formation of reverse micellar–type aggregates of CTADC in nonpolar solvents. In the presence of different ionic and nonionic surfactants, CTADC forms mixed aggregates and controls the reaction due to the charge on the interface and also due to partition of oxidant and substrate in two different domains. High negative entropy of activation (ΔS^? = –145 and –159 J K^?1 mol^?1 in the absence and presence of acetic acid) proposes a more ordered and highly solvated transition state than the reactants. Furthermore, the solvent polarity‐reactivity relationship reveals (i) the presence of less polar and less ionic transition state compared to the reactants during the oxidation, (ii) differential contribution from nonpolar and dipolar aprotic solvents toward the reaction process, and (iii) the existence of polarity/hydrophobic switch at log P = 0.73. A suitable mechanism has been proposed on the basis of experimental results. These results may provide insight into the mechanism of isoniazid oxidation in hydrophobic environment and may assist in understanding the drug resistance in different location.     

Targeting tribbles homolog 3 (TRIB3) protein against type 2 diabetes for the identification of potential inhibitors by in silico screening

Tribbles homolog 3 (TRIB3) protein is inhibiting the insulin signaling by directly binding to the Akt/PKB leading to insulin resistance in the pancreas causing type 2 diabetes mellitus. Hence, TRIB3 protein is considered as a possible drug target for the new lead identification against type 2 diabetes. In the present study, the homology model of TRIB3 protein was generated to explore its biochemical function and molecular interactions in the new lead identification. The energy minimization of TRIB3 protein was carried out and evaluated by validation protocols for structure reliability. The druggable binding site of TRIB3 protein was identified for the virtual screening and molecular docking studies. The Asinex-fragments library of 22634 small molecules was docked at TRIB3 active site using the Glide module to identify new chemical entities. A total of 9 molecules were identified as final hits from virtual screening and their potency was ranked using Glide score, Glide energies, and residues interactions. The 6 prioritized lead molecules were further optimized using AutoDock, Prime MM/GBSA, and percentage of human oral absorption for the identification of potential leads. The molecules L2, L5, and L6 are identified as lead inhibitors and are showing consistent interactions with key residues Glu194 and Lys196 of TRIB3 protein. The identified potential leads were analyzed by ADME properties for their drug likeness and HergIC50 values are predicted for the prevention of preclinical failures. The present work sheds light on the identification of the best lead molecules against TRIB3 protein and offers a route to design as novel potential drug candidates for T2DM.     

In vivo (31)P MRS study of skeletal muscle metabolism in patients with postpolio residual paralysis

The muscle metabolism of at-rest patients with varying degrees of postpolio residual paralysis (PPRP) was studied and compared with that of controls using in vivo phosphorus magnetic resonance spectroscopy. The phosphocreatine (PCr)/inorganic phosphate (Pi) and PCr/adenosine triphosphate ratios were lower in patients than in controls. Reduction in PCr/Pi suggests abnormalities in oxidative phosphorylation. A significant increase was observed in the phosphomonoester/PCr ratio in patients, indicating the accumulation of intermediary compounds of the glycolytic pathway. Furthermore, the phosphodiester/PCr ratio was also significantly increased in patients. In general, the observed changes in metabolite ratios were found to be related to the degree of residual paralysis, suggesting that metabolic changes are secondary to chronic neurogenic processes. These metabolic alterations appear to be the possible cause of energy deficit and underlying muscle fatigue in PPRP patients. The present results provide an insight into the metabolic impairment and degree of muscle damage in patients with PPRP.     

Trypsin Inhibitor from Edible Mushroom Pleurotus floridanus Active against Proteases of Microbial Origin

Protease inhibitors can be versatile tools mainly in the fields of medicine, agriculture and food preservative applications. Fungi have been recognized as sources of protease inhibitors, although there are only few such reports on mushrooms. This work reports the purification and characterization of a trypsin inhibitor from the fruiting body of edible mushroom Pleurotus floridanus (PfTI) and its effect on the activity of microbial proteases. The protease inhibitor was purified up to 35-fold by DEAE-Sepharose ion exchange column, trypsin-Sepharose column and Sephadex G100 column. The isoelectric point of the inhibitor was 4.4, and its molecular mass was calculated as 37 kDa by SDS-PAGE and 38.3 kDa by MALDI-TOF. Inhibitory activity confirmation was by dot-blot analysis and zymographic activity staining. The specificity of the inhibitor toward trypsin was with Ki of 1.043?×?10^?10 M. The inhibitor was thermostable up to 90 °C with maximal stability at 30 °C, active over a pH range of 4–10 against proteases from Aspergillus oryzae, Bacillus licheniformis, Bacillus sp. and Bacillus amyloliquefaciens. Results indicate the possibility of utilization of protease inhibitor from P. floridanus against serine proteases.