Type Of Skeleton Research Articles

Structure Elucidation of Prenyl- and Geranyl-Substituted Coumarins in Gerbera piloselloides by NMR Spectroscopy, Electronic Circular Dichroism Calculations, and Single Crystal X-ray Crystallography.

Crude ethyl acetate extract of Gerbera piloselloides (L.) Cass. was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. This indicated the presence of a series of unprecedented prenyl- and geranyl-substituted coumarin derivatives correlated with both α-glucosidase and PTP1B inhibitory activity. Repeated chromatographic separation targeting these compounds led to the isolation of 13 new compounds, of which ten could be isolated as both enantiomers after chiral separation. The structures of all isolated compounds were characterized by HRMS and extensive 1D and 2D NMR analysis. The absolute configurations of the isolated compounds were determined by comparison of experimental and calculated electronic circular dichroism spectra. Compound 6 features a rare furan-oxepane 5/7 ring system, possibly formed through addition of a geranyl unit to C-3 of 5-methylcoumarin, representing a new type of geranyl-substituted coumarin skeleton. Compounds 19 and 24 are the first examples of dimeric natural products consisting of both coumarin and chromone moieties.

Insights into carbohydrate metabolism from an insulin-like peptide in Macrobrachium rosenbergii

This study identified an insulin-like peptide (ILP) in Macrobrachium rosenbergii termed Mr-ILP and further investigated its function through glucose injection and RNAi. With the analysis of five other glucose metabolism related genes, this study shed light on the molecular mechanism of carbohydrate metabolism in crustaceans. Mr-ILP shared the typical skeleton with six conserved cysteine and mainly expressed in neuroendocrine system. In M. rosenbergii, the elevated hemolymph glucose concentration after glucose injection returned to basal levels in short time, implying an efficient regulatory system in carbohydrate metabolism. Hyperglycemic related genes answered the elevated hemolymph glucose concentration quickly with significant decreased expression level, while Mr-ILP showed delayed response. Instead, glycolysis increased after glucose injection, which indicated glycolysis might play an important role in lowering the abnormally high glucose level. In vivo silencing of Mr-ILP, by injecting the prawns with double-stranded RNA (dsRNA) for 21 days reduced its expression by approximately 75%. Accordingly, glycogen synthase decreased and the trehalose and glycogen level in the hepatopancreas were significantly reduced, indicating the function of Mr-ILP in oligosaccharide and polysaccharide accumulation. When Mr-ILP was silenced, the expression of hyperglycemic related genes were enhanced, but the hemolymph glucose level was not elevated significantly, which might attribute to the increased glycolysis to keep a balanced glucose level in hemolymph.

Meroterpene-Like α-Glucosidase Inhibitors Based on Biomimetic Reactions Starting from β-Caryophyllene.

Background: Natural meroterpenes derived from phloroglucinols and β-caryophyllene have shown high inhibitory activity against α-glucosidase or cancer cells, however, the chemical diversity of this type of skeletons in Nature is limited. Methods: To expand the chemical space and explore their inhibitory activities against α-glucosidase (EC 3.2.1.20), we employed β-caryophyllene and some natural moieties (4-hydroxycoumarins, lawsone or syncarpic acid) to synthesize new types of meroterpene-like skeletons. All the products (including side products) were isolated and characterized by NMR, HR-MS, and ECD. Results: In total, 17 products (representing seven scaffolds) were generated through a one-pot procedure. Most products (12 compounds) showed more potential activity (IC50 < 25 μM) than the positive controls (acarbose and genistein, IC50 58.19, and 54.74 μM, respectively). Compound 7 exhibited the most potent inhibition of α-glucosidase (IC50 3.56 μM) in a mixed-type manner. The CD analysis indicated that compound 7 could bind to α-glucosidase and influence the enzyme’s secondary structure. Conclusions: Compound 7 could serve as a new type of template compound to develop α-glucosidase inhibitors. Full investigation of a biomimic reaction can be used as a concise strategy to explore diverse natural-like skeletons and search for novel lead compounds.

An investigation of the inhibitory mechanism of α-glucosidase by chysalodin from Aloe vera

The aim of our study is to provide new type skeleton of α-glucosidase inhibitor from food source. A new 6′-O-(E)–cinnamoyl-7-methoxy-aloin A (1) was isolated from Aloe vera. Also, known chysalodin (2) was the first report for A. vera. These structures were identified with based on HR-ESI Mass and 1/2D-NMR spectra. These isolated compounds were tested for their inhibitory activities against α-glucosidase by using spectrophotometer. Of these, compound 2 exhibited inhibitory activity, with an IC50 value of 13.4 ± 1.5 μM. An enzyme kinetic study identified the mechanism of binding of the ligand with the enzyme; the ligand binds in the active site of the enzyme in a competitive mode. Additionally, fluorescence quenching between the ligand and receptor revealed a two-to-one reaction. Finally, this finding provides that anthraquinone dimer (2) could be a starting point for the design of new class of α-glucosidase inhibitor.

A comprehensive study on narcissus tazetta subsp. tazetta L.: Chemo-profiling, isolation, anticholinesterase activity and molecular docking of amaryllidaceae alkaloids

Galanthamine, is the most known Amaryllidaceae alkaloid, which is currently being prescribed for the treatment of mild to moderate Alzheimer's disease (AD) due to its anti-acetylcholinesterase activity. Narcissus L., a genus belonging to the same family, has been subjected to intensive research owing to its broad alkaloidal range.The main objective of the present study was to evaluate Narcissus tazetta L. in terms of its therapeutic potential in AD and to isolate Amaryllidaceae alkaloids with anticholinesterase activity.A qualitative determination of the alkaloidal contents of aerial parts and bulbs of the plant were carried out via Gas chromatography–mass spectroscopy (GC–MS) analysis. Additionally, secondary metabolites were isolated from the ethanolic extract of the plant by means of chromatographic methods. The structural elucidation of isolated compounds was established by spectroscopic techniques. Determination of acetylcholinesterase and butyrylcholinesterase inhibitory activities of the isolated Amaryllidaceae alkaloids were accomplished using a microplate assay modified from Ellman's method. These compounds were also subjected to docking studies to determine the non-covalent interactions formed with the active site residues of cholinesterase enzymes.GC–MS monitoring on the profile of N. tazetta was resulted in the detection of 22 alkaloids. Isolation process on the plant has led to isolate four alkaloids belonging to three different skeleton types. Nuclear Magnetic Resonance (NMR) and MS findings verified that those compounds were identical with (−)-9-O-methylpseudolycorine, (−)-narcissidine, (−)-pancratinine-C and (+)-9-O-demethyl-2-α-hydroxyhomolycorine. Among those; 11-hydroxygalanthine and narcissidine have shown significant acetylcholinesterase (AChE) inhibitory activity based on our bioactivity results. It was observed that the docking scores were found close in general, when the docking scores of the isolated alkaloids calculated inside electric eel acetylcholinesterase (eeAChE) and Equus caballus butyrylcholinesterase (eqBuChE) were examined. Increased anti-acetylcholinesterase activity was observed in lycorine-type.This is the first report on the isolation of (−)-pancratinine-C from the genus Narcissus. Docking scores of all the compounds isolated from the title plant were agreeable with the bioactivity results. The evaluation of the results given in this study, reveals that this particular Turkish Narcissus species represents a promising source of bioactive alkaloids with intriguing chemical structures which may have the potential to be drug leads.

Phomeroids A and B: two novel cytotoxic meroterpenoids from the deep-sea-derived fungus Phomopsis tersa FS441

Phomeroids A (1) and B (2), two novel meroterpenoids representing two types of skeletons, together with one known homologous analogue (3) were isolated from the deep-sea-derived fungus Phomopsis tersa FS441.

Regioselective SNAr reaction of the phenoxathiin-based thiacalixarene as a route to a novel macrocyclic skeleton.

The sulfonyl analogue of phenoxathiin-based thiacalix[4]arene, easily accessible from the parent thiacalix[4]arene, reacts with sodium alkoxides to yield a cleaved product representing a novel type of macrocyclic skeleton with a quasi-calixarene structure. As shown by comparison with other derivatives, the internal strain imposed by the heterocyclic moiety is a driving force of this SNAr reaction.

WITHDRAWN: Design, synthesis and bioassay of the (Z)-3-benzylideneisobenzofuran-1(3H)-one derivatives as monoamine oxidase inhibitors

Abstract A series of substituted (Z)-3-benzylideneisobenzofuran-1(3H)-ones have been designed, synthesized, and biologically evaluated in vitro on human monoamine oxidase A/B (hMAO-A/B). Some compounds were potent to inhibit hMAO-B isoenzyme. Especially compound 20 showed an IC50 value of 8.4 nM and a selectivity index more than 1000 folds. Docking experiments and molecular dynamic simulation results showed that this series might bind to the active pocket in the catalytic center and stabilize the protein. This work provided a new type of skeleton for MAO-B inhibitor design, which might benefit the development of Parkinson's disease medicine.

Chemodiversity, chemotaxonomy and chemoecology of Amaryllidaceae alkaloids.

The Amaryllidaceae alkaloids are a distinctive chemotaxonomic feature of the subfamily Amaryllidoideae of the family Amaryllidaceae, which consists of 59 genera and >800 species distributed primarily in tropical and subtropical areas. Since the first isolation, ca. 140 ago, >600 structurally diverse Amaryllidaceae alkaloids have been reported from ca. 350 species (44% of all species in the subfamily). A few have been found in other plant families, but the majority are unique to the Amaryllidoideae. These alkaloids have attracted considerable research interest due to their wide range of biological and pharmacological activities, which have been extensively reviewed. In this chapter we provide a review of the 636 structures of isolated or tentatively identified alkaloids from plants of the Amaryllidoideae and their classification into 42 skeleton types, as well as a discussion on their distribution, and chemotaxonomical and chemoecological aspects.

Development of innovative working bodies of tillage machines

It was shown that plow working bodies for cutting the soil layer of composite structures are now increasingly used. Authors developed new composite working bodies for domestic plows and conducted fi eld operational tests. Authors also produced a batch of experienced new working bodies. There was applied promising steel having a tensile strength after heat treatment of more than 1580 MPa. Authors increased wear resistance of the blade frame and bits hardening hard alloy method of plasma surfacing. There was developed overhead retractable chisel, increasing the resource of the working body by an additional 25–40 %. There was improved geometry of the blade part was achieved by creating a curved surface of the front side of the involute type skeleton. It showed that on diff erent types of soils, experienced plowshares surpassed the serial resource from 2.0 to 4 or more times. It was established that the most metal-intensive and expensive part of the working body, the skeleton, in most cases, with the maximum operating time of the entire product has a working condition, and for further operation it is enough to replace a cheaper replaceable chisel. It was shown that the advantage of experimental working bodies with an overhead chisel over serial ones is the wear on medium soils with a hardness of up to 3.2 MPa per day 1.8–2.2 times, on heavy, hardness more than 4 MPa in 2.5–4.0 times.

The Review of Chemistry, Pharmacology and Processing Method of Rhubarb (Rheum species)

Rhubarb is one of the Chinese traditional medicines. About ninety-four compounds with five different types of skeletons (anthraquinone, anthrones, stilbenes, flavonoids and acylglucosides) have been isolated from rhubarb so far. These constituents are effective in purgative, clearing heat-fire, removing toxic materials from the body, cooling blood and promoting blood circulation. Recent studies have shown that the appropriate processing methods may directly impact on its nutraceutical activities and chemical compositions. Here, we summarize the update progress in the chemical compositions, pharmacological activities and processing methods of rhubarb.

Spatiotemporal characterization of microdamage accumulation and its targeted remodeling mechanisms in diabetic fatigued bone

The skeleton of type 1 diabetes mellitus (T1DM) has deteriorated mechanical integrity and increased fragility, whereas the mechanisms are not fully understood. Load-induced microdamage naturally occurs in bone matrix and can be removed by initiating endogenous targeted bone remodeling. However, the microdamage accumulation in diabetic skeleton and the corresponding bone remodeling mechanisms remain poorly understood. Herein, streptozotocin-induced T1DM rats and age-matched non-diabetic rats were subjected to daily uniaxial ulnar loading for 1, 4, 7, and 10 days, respectively. The SPECT/CT and basic fuchsin staining revealed significant higher-density spatial accumulation of linear and diffuse microdamage in diabetic ulnae than non-diabetic ulnae. Linear microcracks increased within 10-day loading in diabetic bone, whereas peaked at Day 7 in non-diabetic bone. Moreover, diabetic fatigued ulnae had more severe disruptions of osteocyte canaliculi around linear microcracks. Immunostaining results revealed that diabetes impaired targeted remodeling in fatigued bone at every key stage, including increased apoptosis of bystander osteocytes, decreased RANKL secretion, reduced osteoclast recruitment and bone resorption, and impaired osteoblast-mediated bone formation. This study characterizes microdamage accumulation and abnormal remodeling mechanisms in the diabetic skeleton, which advances our etiologic understanding of diabetic bone deterioration and increased fragility from the aspect of microdamage accumulation and bone remodeling.

A 6/5/5/7 heterotetracyclic indole derivative alkaloid isolated from Typhonium giganteum

Typhoniumoid A (1), a new skeleton type alkaloid which was similar to carboline, possessed a 6/5/5/7 heterotetracyclic fused coupling with an unprecedented 7,5-spirocyclic moiety was isolated from Typhonium giganteum Engl. The structure was completely elucidated by combination of diverse methods which include one and two dimensional NMR, and ECD calculations.

Biocompatible and Biodegradable 3D Double-Network Fibrous Scaffold for Excellent Cell Growth.

Fibrous scaffold could provide extracellular matrix (ECM) like structure and desired network for cell growth; however, the mechanical performance of this type uni-structured fibrous scaffold cannot meet the requirement of tissue formation. Therefore, new strategies are needed for form mechanical strength enhancement. In this study, we developed three dimensional double-network structured fibrous scaffold (3D DN-Fs) using self-assembly technology combined with electrospinning technology. Our 3D DN-Fs consists of two types of skeletons: the finer silk nanofibers which can mimic biocompatible ECM structure; and the larger skeletal fibrous layers can greatly improve the mechanical strength and cellular loading ability, and provide good nutrition and excreta delivery system for cell growth. Therefore, our 3D DN-Fs displayed excellent mechanical performance (more than 50% increment), biocompatibility, biodegradability, and a desirable microenvironment for cell growth. More importantly, cultured cells exhibited excellent viability and 3D growth. Our novel strategy greatly enhances the potential application of fibrous scaffold in the biomedical area, such as 3D cell culture and tissue engineering.

The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review.

Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine-sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, β-galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep-inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]-AEA metabolism, kinases, and DNA polymerase β1 . Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.

Squaraine dyes containing diphenylamine group: Effects of different type structures on material properties and organic photovoltaic performances

Four donor-acceptor-donor (D-A-D’) unsymmetrical squaraines (USQs) with different molecular skeletons (XZ-type and YZ-type), containing diphenylamine group with/without methoxy substituent were synthesized as donor materials in bulk-heterojunction (BHJ) organic photovoltaics (OPVs). The introduction of methoxy group in USQs has little different effects on the overall photovoltaic performance. Conversely, the different molecular skeleton types of the USQs have significant influence on their material properties and photovoltaic performances. Compared to BIDPSQ and BIDPOMeSQ with XZ-type molecular skeleton, IDPSQ and IDPOMeSQ with YZ-type molecular skeleton display closer solid-state packing, much lower highest occupied molecular orbital (HOMO) energy level, higher hole mobility and smaller phase separation domain size. Consequently, YZ-type USQs exhibit the most excellent performance with power conversion efficiency (PCE) of ~4%, which is approximately 300% higher than those of XZ-type USQs. Surprisingly, even though IDPSQ and IDPOMeSQ show wide band gaps, the corresponding devices still achieve a highest PCE of ~4%, which is comparable to or even higher than the PCEs of some reported SQ-based devices with low band gaps. These results indicate the YZ-type molecular skeleton and the electron-donating diphenylamine group are very promising to construct highly efficient squaraine donor materials.

Bipolarolides A-G: Ophiobolin-Derived Sesterterpenes with Three New Carbon Skeletons from Bipolaris sp. TJ403-B1.

Bipolarolides A-G (1-7), seven novel ophiobolin-derived sesterterpenes with three new types of skeletons, were characterized from fungus Bipolaris sp. TJ403-B1. Their structures were determined via spectroscopic analyses, X-ray crystallography, and quantum chemical 13 C NMR and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were uniquely defined by a multicyclic caged oxapentacyclo[9.3.0.01,6 .05,9 .18,12 ]pentadecane-bridged system. Compounds 3 and 4 featured an unprecedented 5-5-5-5-fused core skeleton, while 3 also contained an unexpected C-3-C-14 oxygen bridge to construct the caged architecture. Compounds 5-7 form a new class of highly modified pentacyclic oxaspiro[4.4]nonane-containing sesterterpene-alkaloid hybrids. Their biosynthetic pathways and potential HMG-CoA reductase inhibitory and antimicrobial activities are also discussed.

Free vibration and buckling of polymeric shells reinforced with 3D graphene foams

In this paper, free vibration and buckling of polymeric shells reinforced with three-dimensional graphene foams (3D-GrFs) are investigated for the first time. The 3D-GrFs/polymer composites are prepared by infiltrating liquid epoxy resin into the porous structure. Thereinto, three-dimensional graphene foams can distribute uniformly or non-uniformly in the shell thickness direction. The effective Young’s modulus, mass density and Poisson’s ratio are predicted by the rule of mixture. Based on Love’s thin shell theory, governing equations and corresponding boundary conditions are derived by Hamilton’s principle. Then, free vibration and axial buckling of three-dimensional graphene foam reinforced polymer (3D-GrFRP) shells are analyzed by using the Navier method and the Galerkin method. Results show that the 3D-GrF skeleton type, the 3D-GrF skeleton weight fraction, the foam coefficient, the radius-to-thickness ratio, and the length-to-radius ratio play important role on mechanical characteristics of 3D-GrFRP shells.

Study on the equivalence between gas hydrate digital rocks and hydrate rock physical models

According to the filling modes of gas hydrate in the permafrost, combined with rock physical method, two types of hydrate rock physical models are established by the method of elastic modulus model, including skeleton type hydrate rock physical model and fluid type hydrate rock physical model. Besides, based on the CT scanning images of hydrate reservoir rocks, combined with the numerical simulation method of hydrate distribution, two types of hydrate digital rock models are constructed, which correspond to the hydrate rock physical models. Firstly, time average equations are used to estimate several physical properties of hydrate rocks, the velocities of the hydrate rock are calculated on different models, in order to verify the equivalence between hydrate rock physical models and hydrate digital rock models, and compare the difference between different hydrate filling modes. Secondly, different models are appliedto the characteristics analysis of hydrate reservoir rocks. Finally, the theoretical calculation curve is compared with the data of the actual sampling point of the hydrate reservoir, which used to the recognition of hydrate filling modes. It can be seen from the results that there is a good equivalence relationship between the hydrate rock physical models and hydrate digital rock models, and the filling modes of hydrate in this area is more in accordance with the skeleton type models, which means that this method can be used to determine the hydrate filling modes in hydrate reservoirs.

Surgically treated pediatric facial fractures - retrospective study

Background: Facial fractures during pediatric age (<18 years) are mainly caused by sports accidents and interpersonal violence, particullarly in childhood are caused by low energy trauma, and their treatment is related to facial skeleton growth phase and type of injury.