Solid-phase synthesis and biological evaluation of a parallel library of 2,3-dihydro-1,5-benzothiazepines

Solid-phase synthesis of a parallel library of 3'-hydroxy-2,3-dihydrobenzothiazepines has been carried out through [4+3] annulation of alpha,beta-unsaturated ketones with aminothiophenol, using Wang resin as solid support. The synthesized compounds were evaluated for their potential as antibacterial, tumor inhibitors as well as acetyl- and butyrylcholinesterase inhibitors. None of the compounds showed any significant antibacterial activity. However, quite a few compounds showed significant potential as crown gall tumor inhibitors. These results reflect a strong exploratory potential in search of new benzothiazepines as source of anticancer agents. The results of the inhibition of cholinesterase revealed that benzothiazepines have a greater potential as butyrylcholinesterase inhibitors as compared to acetylcholinesterase. Moreover, the substitution of hydroxy group at C-3 in ring A led to increased activity when compared to unsubstituted- and 2'-OH substituted benzothiazepines.     

Biosynthesis of polyhydroxyalkanoates from styrene by <Emphasis Type="Italic">Enterobacter</Emphasis> spp. isolated from polluted environment

Background

Styrene and its metabolites are known to have serious adverse effects on human health and hence, strategies to prevent its release, eradicate it from the environment, and understand its route of degradation are being considered.

Methods

A total of 18 strains were isolated from 4 samples of diesel contaminated soils. Among them 5 strains were selected for their ability to degrade styrene and use it as a sole carbon source to produce PHA. These strains were identified as Enterobacter spp. on the basis of 16S rRNA gene sequencing. Bacteria were screened for their ability to produce PHA by utilizing glucose and styrene as a carbon sources. Screening for PHA production was done by Nile blue A, Sudan black B, and phase contrast microscopy and the selected 3 strains showed positive results. Growth kinetics along with time profiling of PHA was performed for glucose and styrene as carbon sources.

Results

PHA extraction was done at equal intervals of 12 h by sodium hypochlorite method which showed that these strains accumulate maximum amount of PHA after 48 h in glucose (30.60%). FTIR analysis of PHA was done which revealed homopolymer PHB and copolymer (PHB-co-PHV) production in strains by utilizing glucose and styrene. Gas chromatography mass spectrometry was carried out to identify the metabolites produced by bacterial strains grown on styrene. Metabolites of styrene degradation included propyne and phenylalanine. Genomic DNA isolation was carried out to amplify phaC gene which encodes PHA synthase enzyme.

Conclusions

The conversion of styrene to polyhydroxyalkanoates (PHA) provides a new and unique link between an aromatic environmental pollutant and aliphatic PHA accumulation.

     

<Emphasis Type="Italic">Phenylobacterium terrae</Emphasis> sp. nov., isolated from a soil sample of Khyber-Pakhtun-Khwa,Pakistan

A Gram-stain negative, aerobic, motile, non-spore-forming and rod-shaped bacterial strain, designated YIM 730227^T, was isolated from a soil sample, collected from Karak district, Khyber-Pakhtun-Khwa, Pakistan. The bacterium was characterized using a polyphasic taxonomic approach. Pairwise comparison of the 16S rRNA gene sequences showed that strain YIM 730227^T is closely related to Phenylobacterium lituiforme FaiI3^T (97.5% sequence similarity), Phenylobacterium muchangponense A8^T (97.4%), Phenylobacterium panacis DCY109^T (97.1%), Phenylobacterium immobile E^T (97.1%) and Phenylobacterium composti 4T-6^T (97.0%), while also sharing 98.0% sequence similarity with Phenylobacterium hankyongense HKS-05^T after NCBI blast, showing it represents a member of the family Caulobacteraceae. The major respiratory quinone was Q-10 and the major fatty acids were C_16:0, summed feature 8 (comprising C_18:1ω7c and/or C_18:1ω6c), C_18:1ω7c 11-methyl and C_17:0. The polar lipids were phosphatidylglycerol, unidentified glycolipids, phospholipid and unidentified lipid. The G?+?C content of the genomic DNA was 68.2 mol%. The DNA–DNA relatedness values of strain YIM 730227^T with P. hankyongense HKS-05^T, P. lituiforme FaiI3^T, P. muchangponense A8^T, P. panacis DCY109^T, P. immobile E^T and P. composti 4T-6^T were 31.3?±?0.6, 26.1?±?0.2, 24.3?±?0.1, 21.8?±?0.9, 19.8?±?0.6 and 18.2?±?1.1%, respectively, values lower than 70%. Besides the morphological and chemotaxonomic characteristics, phylogenetic analyses of 16S rRNA gene sequences and the biochemical characteristics indicated that the strain YIM 730227^T represents a novel member of the genus Phenylobacterium, for which the name Phenylobacterium terrae sp. nov. (type strain YIM 730227^T =?KCTC62324^T?=?CGMCC 1.16326^T) is proposed.     

Papaya Ring Spot Virus: An Understanding of a Severe Positive-Sense Single Stranded RNA Viral Disease and Its Management

Viral diseases have been studied in-depth for reducing quality, yield, health and longevity of the fruit, to highlight the economic losses. Positive-sense single-stranded RNA viruses are more devastating among all viruses that infect fruit trees. One of the best examples is papaya ringspot virus (PRSV). It belongs to the genus Potyvirus and it is limited to cause diseases on the family Chenopodiaceae, Cucurbitaceae and Caricaceae. This virus has a serious threat to the production of papaya, which is famous for its high nutritional and pharmaceutical values. The plant parts such as leaves, latex, seeds, fruits, bark, peel and roots may contain the biological compound that can be isolated and used in pharmaceutical industries as a disease control. Viral disease symptoms consist of vein clearing and yellowing of young leaves. Distinctive ring spot patterns with concentric rings and spots on fruit reduce its quality and taste. The virus has two major strains P and W. The former cause disease in papaya while the later one in papaya. Virion comprises 94.4% protein, including a 36 kDa coat protein which is a component responsible for a non-persistent transmission through aphids, and 5.5% nucleic acid. Cross protection, development of transgenic crops, exploring the resistant sources and induction of pathogen derived resistance have been recorded as effective management of PRSV. Along with these practices reduced aphid population through insecticides and plant extracts have been found ecofriendly approaches to minimize the disease incidence. Adoption of transgenic crops is a big challenge for the success of disease resistant papaya crops. The aim of this review is to understand the genomic nature of PRSV, detection methods and the different advanced control methods. This review article will be helpful in developing the best management strategies for controlling PRSV.     

Biosorption of Pb(II) from contaminated water onto Moringa oleifera biomass: kinetics and equilibrium studies

Abstract

The present study aims at evaluating a batch scale biosorption potential of Moringa oleifera leaves (MOL) for the removal of Pb(II) from aqueous solutions. The MOL biomass was characterized by FTIR, SEM, EDX, and BET. The impact of initial concentrations of Pb (II), adsorbent dosage, pH, contact time, coexisting inorganic ions (Ca²⁺, Na⁺, K⁺, Mg²⁺, CO₃^2?, HCO₃^?, Cl^?), electrical conductivity (EC) and total dissolved salts (TDS) in water was investigated. The results revealed that maximum biosorption (45.83?mg/g) was achieved with adsorbent dosage 0.15?g/100?mL while highest removal (98.6%) was obtained at adsorbent biomass 1.0?g/100?mL and pH 6. The presence of coexisting inorganic ions in water showed a decline in Pb(II) removal (8.5% and 5%) depending on the concentrations of ions. The removal of Pb(II) by MOL decreased from 97% to 89% after five biosorption/desorption cycles with 0.3?M HCl solution. Freundlich model yielded a better fit for equilibrium data and the pseudo-second-order well described the kinetics of Pb(II) biosorption. FTIR spectra showed that –OH, C–H, –C–O, –C?=?O, and –O–C functional groups were involved in the biosorption of Pb(II). The change in Gibbs free energy (ΔG = ?28.10?kJ/mol) revealed that the biosorption process was favorable and thermodynamically driven. The results suggest MOL as a low cost, environment-friendly alternative biosorbent for the remediation of Pb(II) contaminated water.     

Thin Film Encapsulation of Organic Solar Cells by Direct Deposition of Polysilazanes from Solution

Organic electronic devices (OEDs), e.g., organic solar cells, degrade quickly in the presence of ambient gases, such as water vapor and oxygen. Thus, in order to extend the lifetime of flexible OEDs, they have to be protected by encapsulation. A solution‐based encapsulation method is developed, which allows the direct deposition of the diffusion barrier on top of OEDs, thus avoiding lamination of barrier films. The method is based on the deposition of a perhydropolysilazane (PHPS) ink and its subsequent conversion into a silica layer by deep UV irradiation. The resulting barrier films show water vapor transmission rates (WVTRs) of <10^?2 g m^?2 d^?1 (40 °C/85% relative humidity (RH)) and oxygen transmission rates (OTRs) of <10^?2 cm³ m^?2 d^?1 bar^?1 at ambient conditions. Flexibility of the resulting barrier films is improved by coating a barrier stack of several thin PHPS layers alternating with organic polymer interlayers. These stacks show an increase of WVTR values by less than 10% after 3000 bending cycles. Direct coating of the PHPS films on top of organic solar cells enhances the device lifetime in damp heat conditions from a few hours to beyond 300 h.     

Transgelin: a new gene involved in LDL endocytosis identified by a genome-wide CRISPR-Cas9 screen

A significant proportion of patients with elevated LDL and a clinical presentation of familial hypercholesterolemia do not carry known genetic mutations associated with hypercholesterolemia, such as defects in the LDL receptor. To identify new genes involved in the cellular uptake of LDL, we developed a novel whole-genome clustered regularly interspaced short palindromic repeat-Cas9 KO screen in HepG2 cells. We identified transgelin (TAGLN), an actin-binding protein, as a potentially new gene involved in LDL endocytosis. In silico validation demonstrated that genetically predicted differences in expression of TAGLN in human populations were significantly associated with elevated plasma lipids (triglycerides, total cholesterol, and LDL-C) in the Global Lipids Genetics Consortium and lipid-related phenotypes in the UK Biobank. In biochemical studies, TAGLN-KO HepG2 cells showed a reduction in cellular LDL uptake, as measured by flow cytometry. In confocal microscopy imaging, TAGLN-KO cells had disrupted actin filaments as well as an accumulation of LDL receptor on their surface because of decreased receptor internalization. Furthermore, TAGLN-KO cells exhibited a reduction in total and free cholesterol content, activation of SREBP2, and a compensatory increase in cholesterol biosynthesis. TAGLN deficiency also disrupted the uptake of VLDL and transferrin, other known cargoes for receptors that depend upon clathrin-mediated endocytosis. Our data suggest that TAGLN is a novel factor involved in the actin-dependent phase of clathrin-mediated endocytosis of LDL. The identification of novel genes involved in the endocytic uptake of LDL may improve the diagnosis of hypercholesterolemia and provide future therapeutic targets for the prevention of cardiovascular disease.