Prenylated flavonoids, a unique class of flavonoids which combine a flavonoid skeleton and a lipophilic prenyl side-chain, possess great potential biological activities including cytotoxicity, ...anti-inflammation, anti-Alzheimer, anti-microbial, anti-oxidant, anti-diabetes, estrogenic, vasorelaxant and enzyme inhibition. Recently, prenylated flavonoids have become an indispensable anchor for the development of new therapeutic agents, and have received increasing from medicinal chemists. The prenylated flavonoids have been outstanding developed through isolation, semi or fully synthesis in a very short period of time, which proves the great value in medicinal chemistry researches. In this review, research progress of prenylated flavonoids including natural prenylated flavonoids, structural modification, synthetic methodologies and pharmacological activities was summarized comprehensively. Furthermore, the structure–activity relationships (SARs) of prenylated flavonoids were summarized which provided a basis for the selective design and optimization of multifunctional prenylated flavonoid derivatives for the treatment of multi-factorial diseases in clinic.
Display omitted
•This article provides over 500 natural and synthetic prenylated flavonoids from 2000 to 2021.•The diverse activities and structure–activity relationships of prenylated flavonoids are summarized.•The synthetic methodologies of prenylated flavonoids are summarized.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Display omitted
•Most GTF hybrids exhibited strong inhibitory effect on Aβ aggregation and potent butyrylcholinesterase inhibitory potencies.•GTF cinnamate derivative A15 exhibited best inhibition of ...Aβ aggregation and potent AChE inhibitory activity.•GTF triazole derivative C4 showed the best inhibitory activity to BuChE.•A15 and C4 showed potent neuroprotective activities and nearly no toxicity on SH-SY5Y cells.
7-O-galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer’s disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β-amyloid (Aβ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of Aβ aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC50, 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC50, 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood–brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H2O2-induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multiple studies have confirmed that acid sphingomyelinase (ASM) activity is associated with depression. The discovery of direct inhibitors against ASM is of great significance for exploring ...antidepressants and their mechanisms of action. Herein, a series of novel phenylpyrazole analogues were rationally designed and synthesized. Among them, compound 46 exhibited potent inhibitory activity (IC50 = 0.87 μM) and good drug-like properties. In vivo studies demonstrated that compound 46 was involved in multiple antidepressant mechanisms of action, which were associated with a decline of ceramide, including increasing the Bcl-2/Bax ratio and BDNF expression, down-regulating caspase-3 and caspase-9, ameliorating oxidative stress, reducing the levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6, and elevating 5-HT levels in the brains of mice, respectively. These meaningful results reveal for the first time that direct inhibitors exhibit remarkable antidepressant effects in the CUMS-induced mouse model through multiple mechanisms of antidepressant action.
Two series of flavonoid hybrids, totaling 42 compounds, were designed, synthesized and evaluated to develop antiviral compounds effective against hepatitis A virus (HAV). A recombinant viral ...screening system revealed that most of the synthesized derivatives exhibited significant anti-HAV activity, and compounds B2, B3, B5 and B27 were identified as potential inhibitors of HAV. Post-treatment of cells with B2, B3, B5 and B27 after HAV infection strongly suppressed HAV infection, whereas pretreatment or simultaneous treatment were ineffective. Furthermore, these four compounds significantly inhibited HAV (HM175/18f strain) production in a dose-dependent manner. Analyses using HAV subgenomic replicon systems indicated that these compounds specifically inhibit HAV RNA replication. More importantly, the most potent compounds B2 and B27 also showed clear inhibitory effects on two other HAV strains, KRM031 and TKM005, which also isolated from clinical patients. Our study is the first to report these newly designed flavonoid hybrids as lead compounds for the development of novel anti-HAV drugs.
Display omitted
•Flavonoid hybrids were synthesized as anti-HAV candidate agents.•HAV/NLuc system was used to screen anti-HAV agents.•B2, B3, B5 and B27 inhibit HAV production against viral replication.•B2 and B27 suppressed two different HAV stains isolated from hepatitis A patients.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Developing low-cost, high-activity transition metal-based oxygen reduction electrocatalysts to replace noble metals in oxygen reduction reactions continues to pose a notable difficulty in the field ...of research. In this work, a straightforward approach was employed to fabricate Fe, Co, Ni-encapsulated zeolite imidazolate framework (ZIF8) precursors, which were later subjected to pyrolysis to yield carbon-coated FeCoNi nanoparticles (FeCoNi/NC). The obtained FeCoNi/NC catalyst exhibited irregularly distributed nanotubes with abundant active sites on its surface. The electrochemical experiments conducted revealed that the oxygen reduction reaction in an alkaline electrolyte exhibited a half-wave potential of 0.84 V (
vs.
RHE), which is similar to that of the commercially available Pt/C. The self-made Zn-air battery displayed a narrow discharge voltage gap (0.77 V) and exhibited good cycling stability. These findings provide significant contributions to the understanding and development of multi-metallic electrocatalysts derived from zeolite imidazolate frameworks (ZIFs).
Developing low-cost, high-activity transition metal-based oxygen reduction electrocatalysts to replace noble metals in oxygen reduction reactions continues to pose a notable difficulty in the field of research.
Display omitted
•Two pairs of new enantiomeric phenylpropanoids and lignans were isolated from Prunus tomentosa seeds.•The absolute configurations of isolated enantiomers were determined by ...theoretical ECD calculation.•All optical pure compounds showed high inhibitory activity on β-amyloid aggregation.•Docking simulation study exhibits that the Gln15 may be a key active site of anti-Aβ1–42 aggregation.
Alzheimer’s disease (AD) is characterized by the progressive accumulation of extracellular β-amyloid (Aβ) aggregates. Recently, lignans and phenylpropanoids are attracting increasing attention to discovery useful agents of inhibition on Aβ aggregation. In the present study, to develop potential agents for slowing the progression of AD, Prunus tomentosa seeds were selected as a raw material for bioactive compounds, which led to the separation of two pairs of new enantiomeric lignans and phenylpropanoids using chiral HPLC. The planar structures of these compounds were elucidated by spectroscopic data analyses. And their absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The biosynthesis pathway was also discussed. Additionally, the inhibitory activity on Aβ aggregation of all optical pure compounds was tested by thioflavin T (ThT) assay. The isolates (1a, 1b, 2a and 2b) showed more potent inhibitory activity than positive control curcumin with inhibitory rate of 73.89 ± 3.41% 78.69 ± 1.50%, 63.25 ± 2.68%, and 67.13 ± 0.90% at 20 μM, respectively. More importantly, the inhibition profiles were explained by molecular dynamics and docking simulation studies.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Data pre-deployment in the HDFS （Hadoop distributed file systems） is more complicated than that in traditional file systems. There are many key issues need to be addressed, such as determining the ...target location of the data prefetching, the amount of data to be prefetched, the balance between data prefetching services and normal data accesses. Aiming to solve these problems, we employ the characteristics of digital ocean information service flows and propose a deployment scheme which combines input data prefetching with output data oriented storage strategies. The method achieves the parallelism of data preparation and data processing, thereby massively reducing I/O time cost of digital ocean cloud computing platforms when processing multi-source information synergistic tasks. The experimental results show that the scheme has a higher degree of parallelism than traditional Hadoop mechanisms, shortens the waiting time of a running service node, and significantly reduces data access conflicts.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A significant advance toward the design and fabrication of a novel hierarchical supercapacitor electrode consisting of FeCo2S4‐tubes with well‐defined square cross‐section and intersecting nanosheets ...built porous shells on a 3D porous Ni backbone via controlled sulfidation is reported. This general method allows template‐free synthesis of metal sulfides tubular structures with polygonal cross‐sections and also fine control over the nanostructure leading to both maximized porosity and saturation sulfidation. New insights into concentration and time dependent sulfidation reaction kinetics are proposed. The FeCo2S4 electrode achieves a specific capacitance reaching 2411 F g‐1 at 5 mA cm‐2 and good rate capability, which are superior over those for nanotube arrays of other ternary transition metal sulfides. This is attributed to rich redox reactions, the highly porous but robust architecture as well as high electrical conductivity. Especially such porous shells effectively avoid “dead volume”, thus improve the utilization ratio of the electrode material. Asymmetric solid‐state device applying the FeCo2S4 as positive electrode and N‐doped graphene hydrogel film as negative electrode has a high cell voltage of 1.6 V and thus delivers considerably higher energy density of 76.1 W h kg‐1 (at 755 W kg‐1) than those reported for similar devices.
General controlled sulfidation results in a novel hierarchical supercapacitor electrode consisting of FeCo2S4‐tubes with well‐defined square cross‐section and intersecting nanosheets built porous shells on a 3D porous Ni backbone, which shows high specific capacitances, good rate‐capability and excellent cycling‐stability due to the highly porous but robust architecture, rich redox reactions as well as high conductivity.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To achieve high‐performance wearable supercapacitors (SCs), a new class of flexible electrodes with favorable architectures allowing large porosity, high conductivity, and good mechanical stability ...is strongly needed. Here, this study reports the rational design and fabrication of a novel flexible electrode with nanotube‐built multitripod architectures of ternary metal sulfides' composites (FeCo2S4–NiCo2S4) on a silver‐sputtered textile cloth. Silver sputtering is applicable to almost all kinds of textiles, and S2− concentration is optimized during sulfidation process to achieve such architectures and also a complete sulfidation assuring high conductivity. New insights into concentration‐dependent sulfidation mechanism are proposed. The additive‐free FeCo2S4–NiCo2S4 electrode shows a high specific capacitance of 1519 F g−1 at 5 mA cm−2 and superior rate capability (85.1% capacitance retention at 40 mA cm−2). All‐solid‐state SCs employing these advanced electrodes deliver high energy density of 46 W h kg−1 at 1070 W kg−1 as well as achieve remarkable cycling stability retaining 92% of initial capacitance after 3000 cycles at 10 mA cm−2, and outstanding reliability with no capacitance degradation under large twisting. These are attributed to the components' synergy assuring rich redox reactions, high conductivity as well as highly porous but robust architectures. An almost linear increase in capacitance with devices' area indicates possibility to meet various energy output requirements. This work provides a general, low‐cost route to wearable power sources.
The use of silver‐sputtered textile cloth and optimized S2− concentration during sulfidation results in a novel flexible electrode with FeCo2S4–NiCo2S4 composite nanotube‐built multitripod architectures, which shows high specific capacitances and superior rate capability. All‐solid‐state supercapacitors employing these electrodes have high energy density, remarkable cycling stability, and outstanding reliability with no capacitance degradation under large twisting.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The early Paleozoic sediments document two major biological events: the Great Ordovician Biodiversification Event (GOBE) and Late Ordovician mass extinction (LOME). Many investigations have focused ...on taxonomic richness patterns during these major diversification and extinction events, providing insights into their timings and potential causes. However, the coarse temporal resolutions used in previous investigations hampered their ability to document fine-scale patterns. To address these issues, we employed CONOP analysis to data collected from a large suite of southern Chinese stratigraphic successions to construct a high-resolution (temporal resolution of ~21.0 Kyr) regional chronostratigraphy and document species richness dynamics during the middle–late Cambrian to early Silurian interval. Our results showed that the GOBE began in the early Tremadocian and ended at the Dapingian–Darriwilian boundary and consisted of two major radiation phases. The main pulse of GOBE, which lasted from the late Floian to the earliest Darriwilian, exhibited a species richness increase with elevated origination and extinction rates. Major marine groups showed no significant diachroneity during the GOBE, with most presenting richness peaks in this event's main pulse of the GOBE. Plankton demonstrated a significant diversification from the late Cambrian to the GOBE climax and subsequently dominated the marine realm in South China. Marine life experienced two extinction events in the Late Ordovician, the Katian extinction and Hirnantian extinction, which resulted in a regional species loss of ~67%.
•38,122 local records of 2986 species to construct the early Paleozoic biodiversity history•The biodiversity curve achieves a resolution of ~21.0 Kyr by using CONOP and supercomputer.•GOBE showed a two-phased exponential richness increase of ~9.9 times in ~16.6 Myr.•Two extinctions in the Late Ordovician eliminated ~67% marine species.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
