RNA helicases are the largest group of enzymes in eukaryotic metabolism. The DEXD/H-box putative form helicase superfamily II, whose members defined by seven highly conserved amino acid motifs, making specific targeting selected a challenging pharmacological problem. translation initiation factor eIF4A is prototypical DEAD-box that works conjunction with eIF4B and eIF4H as subunit eIF4F to prepare mRNA template for ribosome binding, possibly unwinding secondary structure proximal 5′ m 7...

Abstract Peloruside A (peloruside), a microtubule-stabilizing agent from marine sponge, is less susceptible than paclitaxel to multidrug resistance arising overexpression of the P-glycoprotein efflux pump and not affected by mutations that affect taxoid binding site β-tubulin. In vitro studies with purified tubulin indicate peloruside directly induces polymerization in absence microtubule-associated proteins. Competition for between peloruside, paclitaxel, laulimalide revealed binds...

Abstract Molecular representations have essential roles in bio-cheminformatics as they facilitate the growth of machine learning applications numerous sub-domains biology and chemistry, especially drug discovery. These transform structural chemical information molecules into machine-readable formats that can be efficiently processed by computer programs. In this paper, we present a comprehensive review, providing readers with diverse perspectives on strengths weaknesses well-known molecular...

Background The multiparameter fluorometric analysis of intact and fixed cells often requires the use a nuclear DNA discrimination signal with spectral separation from visible range fluorochromes. We have developed novel deep red fluorescing bisalkylaminoanthraquinone, DRAQ5 (Exλmax 646 nm; Emλmax 681 Emλrange 665–>800 nm), high affinity for capacity to enter living cells. describe here characteristics applications this synthetic compound, particularly in relation cytometric cell cycle....

Smoking is a main cause of premature death and preventable disease in the world. Interestingly, animal studies indicate that inhibition monoamine oxidase (MAO), key enzymes for degradation neurotransmitters, increased self-administration nicotine. The purpose this study was to identify characterize potential MAO inhibitors tobacco smoke responsible smokers. A bioassay-guided isolation from an extract showed catechol, 4-methylcatechol, hydroquinone, α-linolenic acid, linoleic acid all...

The bioactive resorcylic acid lactone aigialomycin D (1) has been synthesized by a novel combination of ring-closing metathesis (RCM) and Ramberg−Bäcklund reactions. This synthetic strategy enables the C1′−C2′ alkene to be masked as sulfone during formation macrocycle ring closing at C7′−C8′ olefin, thus avoiding competing cyclohexene. A subsequent reaction efficiently produces E-alkene. combined RCM/Ramberg−Bäcklund should widely applicable synthesis macrocyclic dienes.

Piliostigma thonningii, Ocimum gratissimum, Nauclea latifolia and Alstonia boonei are used in Nigerian traditional medicines against gastrointestinal helminths of animals man. Proanthocyanidins were detected Nauclea, but not or Ocimum. Extracts these plants killed 50% brine shrimp nauplii at <10 ppm (Nauclea), 100 (Piliostigma) <1000 (Ocimum Alstonia), the LD50 being similar to anthelmintic drug piperazine. also toxic parasitic nematode Haemonchus infective L3 stage. Nematode...

The phase II detoxification system glutathione transferase (GST) is associated with the establishment of parasitic nematode infections within gastrointestinal environment mammalian host. We report functional analysis a GST from an important worldwide small ruminants, Haemonchus contortus. This shows limited activity range classical substrates but effectively binds hematin. high-affinity binding site for hematin was not present in showing most identity, CE07055 free-living Caenorhabditis...

A novel series of 1,4-disubstituted chloroethylaminoanthraquinones, containing alkylating chloroethylamino functionalities as part a rigid piperidinyl or pyrrolidinyl ring-system, have been prepared. The target compounds were prepared by ipso-displacement halides various anthraquinone chromophores either hydroxylated chlorinated piperidinyl- pyrrolidinyl-alkylamino side chains. chloroethylaminoanthraquinones shown to alkylate guanine residues linearized pBR322 (1−20 μM), and two...

Addition reactions to a 3,4-anhydroheptanose gave heptanoside analogues of carbohydrate derivatives in good excellent stereochemical purity. Characterization the products by (1)H and (13)C NMR, COSY, HSQC-DEPT, HMBC, 1D TOCSY, NOE experiments were performed obtain stereochemistry addition. The used this study is obtained from ring-expansion cyclopropanated galactal thus demonstrates synthetic utility heptanose synthesis via carbohydrates.

Drugs that target microtubules are a successful class of anti-cancer agents have been in clinical use for over two decades. Acquired resistance to these drugs, however, remains serious problem. Microtubule alterations, such as tubulin mutations and altered β- isotype expression, prominent factors development resistance. Changes actin intermediate filament proteins can also mediate sensitivity microtubule-targeting drugs. This review focuses on the mechanisms by which alterations cytoskeletal...

A recombinant glutathione S-transferase (GST) (EC 2.5.1.18) from the parasitic nematode Ascaris suum(AsGST1) displays specific activity with a variety of model substrates and secondary products lipid peroxidation. The AsGST1 interacts range inhibitors, haematin-related compounds, bile acids anthelminthics. reported variations in biochemical correlate structural differences observed by homology modelling. Here, topography proposed substrate binding site between host GSTs were identified....

The activity of the epithelial Na+ channel (ENaC) is required for maintenance salt and water balance in body. Channel regulated by ubiquitin-protein ligase Nedd4 ['neuronal precursor cell-expressed developmentally down-regulated (gene 4)'] that interacts with via its WW domains. Mutations subunits disrupt this interaction cause Liddle's syndrome, a severe inherited form hypertension. In previous studies we showed domains 2, 3 4 human bound to ENaC (hENaC) subunits, whereas domain 1 did not....

Background The epithelial sodium channel (ENaC) is an integral component of the pathway for Na+ absorption in cells. ubiquitin ligases Nedd4 and Nedd4-2 bind to ENaC decrease its activity. Conversely, Serum- Glucocorticoid regulated Kinase-1 (SGK1), a downstream mediator aldosterone, increases This effect at least partly mediated by direct interaction between SGK Nedd4-2. binds both Nedd4-2, but it only able phosphorylate Phosphorylation reduces ability ENaC, due phosphorylated with 14-3-3...

Two new peloruside congeners (3 and 4) were isolated from wild aquacultured collections of the New Zealand marine sponge Mycale hentscheli. Small-scale reactions on A (1) have been performed, which along with isolation 3 4, give further insight into bioactive pharmacophore 1.

The physical characterisation, capture and detection of extracellular vesicles (EVs) exosomes derived from breath condensate is reported. Breath-derived EVs were isolated captured on a gold substrate using two complimentary methods. characterised detected surface plasmon resonance (SPR) electrochemical impedance spectroscopy (EIS). EIS was done aptamers as targeting moiety showed larger change in resistance between dilute concentrations (less than 7 μg/mL).This the first report breath. In...

The activity of the epithelial Na+ channel (ENaC) is required for maintenance salt and water balance in body. Channel regulated by ubiquitin-protein ligase Nedd4 ['neuronal precursor cell-expressed developmentally down-regulated (gene 4)'] that interacts with via its WW domains. Mutations subunits disrupt this interaction cause Liddle's syndrome, a severe inherited form hypertension. In previous studies we showed domains 2, 3 4 human bound to ENaC (hENaC) subunits, whereas domain 1 did not....

N-4,4-Dimethyl-2,6-dioxocyclohexylidenemethyl (Dcm) amino acids are readily prepared and the protecting group can be removed with hydrazine at room temperature; their potential in solid phase peptide synthesis is illustrated.