An Innovative Sb-W-Cotemplated Antimonotungstate with Potential in Sensing Paroxetine Electrochemically.

Advances in polyoxometalate (POM) self-assembly chemistry are always accompanied by new developments in molecular blocks. The exploration and discovery of uncommon building blocks offer great possibilities for generating unprecedented POM clusters. An intriguing Sb-W-cotemplated antimonotungstate [HN(CH)]Na[SbWO]Er(HO)Sb[SbWWO]·22HO () was synthesized, which comprises a classical trivacant Keggin [SbWO] ({SbW}) fragment and an unclassical lacunary Dawson-like [SbWWO] ({SbWW}) subunit.

Heterobifunctional Cross-Linker with Dinitroimidazole and -Hydroxysuccinimide Ester Motifs for Protein Functionalization and Cysteine-Lysine Peptide Stapling.

A heterobifunctional cross-linker with one sulfhydryl-reactive dinitroimidazole end and another amine-reactive -hydroxysuccinimide (NHS) ester end was designed and synthesized. The two motifs of this cross-linker, dinitroimidazole and NHS ester, proved to react with thiol and amine, respectively, in an orthogonal way. The cross-linker was further applied to construct stapled peptides of different sizes and mono- and dual functionalization (including biotinylation, PEGylation, and fluorescence labeling) of protein.

Dual functional antioxidant and butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of novel melatonin-alkylbenzylamine hybrids.

Here, we have designed and synthesized a series of melatonin-alkylbenzylamine hybrids as multitarget agents for the treatment of Alzheimer's disease (AD). Most of them exhibited a potent multifunctional profile involving cholinesterase inhibition and antioxidant effects. Among these compounds, compound 5 was most the potent antioxidant (ORAC = 5.

Organophosphonic Acid-Regulating Assembly of P-Sb Polyoxotungstate and Its Potential in Building a Dual-Signal Readout Electrochemical Aptasensor for Carcinogen Detection.

Template-directed assembly of giant cluster-based nanomaterials is an everlasting theme in cluster science. In this work, ethylenediamine tetramethylphosphonic acid [HEDTPA = (POCH(OH))CHN] and [B-α-SbWO] were, respectively, used as an organic template and an inorganic template to prepare an organophosphonic acid-regulating P-Sb-heteroatom-inserted polyoxotungstate aggregate [HN(CH)]NaH[CeWO(HEDTPA)SbWO][B-α-SbWO]·36HO (). Noteworthily, organophosphonic acid ligand not only works as an organic template leading to the assembly of a [HEDTPASbWO] building block but also further bridges the sandwich-type [CeWO(B-α-SbWO)] entity.

A multi-target directed ligands strategy for the treatment of Alzheimer's disease: Dimethyl fumarate plus Tranilast modified Dithiocarbate as AChE inhibitor and Nrf2 activator.

Alzheimer's disease (AD) possessed intricate pathogenesis. Currently, multi-targeted drugs were considered to have the potential to against AD by simultaneously triggering molecules in functionally complementary pathways. Hence, a series of molecules based on the pharmacophoric features of Dimethyl fumarate, Tranilast, and Dithiocarbate were designed and synthesized.

Design, Synthesis and Anti-Tumor Activity Evaluation of Novel 3,4-(Methylenedioxy)cinnamic Acid Amide-Dithiocarbamate Derivatives.

The fragments, 3,4-(methylenedioxy)cinnamic acid amide and dithiocarbamates, have received increasing attention because of their multiple pharmacological activities in recent years, especially in anti-tumor. We synthesized 17 novel 3,4-(methylenedioxy)cinnamic acid amide-dithiocarbamate derivatives based on the principle of pharmacophore assembly and discovered that compound 4a displayed the most potent antiproliferative activity against HeLa cells with IC value of 1.01 μM.

Design, Synthesis and Biological Evaluation of New 3,4-Dihydro-2(1)-Quinolinone-Dithiocarbamate Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports.

Purpose: To obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1)-quinolinone and dithiocarbamate.

Ellis Fruit Extracts Attenuated Colitis in 2,4,6-Trinitrobenzenesulfonic Acid-Induced Rats.

Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction.

Polymyxin B-inspired non-hemolytic tyrocidine A analogues with significantly enhanced activity against gram-negative bacteria: How cationicity impacts cell specificity and antibacterial mechanism.

Naturally occurring cyclic antimicrobial peptides (AMPs) such as tyrocidine A (Tyrc A) and gramicidin S (GS) are appealing targets for the development of novel antibiotics. However, their therapeutic potentials are limited by undesired hemolytic activity and relatively poor activity against Gram-negative bacteria. Inspired by polycationic lipopeptide polymyxin B (PMB), the so called 'last-resort' antibiotic for the treatment of infections caused by multidrug-resistant Gram-negative bacteria, we synthesized and biologically evaluated a series of polycationic analogues derived from Tyrc A.

Tricarboxylic-Ligand-Decorated Lanthanoid-Inserted Heteropolyoxometalates Built by Mixed-Heteroatom-Directing Polyoxotungstate Units: Syntheses, Structures, and Electrochemical Sensing for 17β-Estradiol.

Organic-inorganic hybrid metal-oxide clusters have been pursued for many years, benefiting from their abundant structures and prominent performances. Upon our exploration, a family of unusual mixed-heteroatom (Sb, P)-directing lanthanoid (Ln)-inserted heteropolyoxotungstates (Ln-HPOTs), [(CH)NH]NaH[Ln(HP)W(HO)(Hptca)O][SbWO]·27HO [Ln = Ce (), La (), Pr ()], functionalized by 1,2,3-propanetricarboxylic acid (Hptca) was achieved. The intriguing trimeric [Ln(HP)W(HO)(Hptca)O][SbWO] polyanion was established by two trivacant [B-α-SbWO] segments mounted on both sides and one rare [HPWO] segment at the bottom, which are bridged via an organic-inorganic hybrid [WLn(HO)O(Hptca)] central moiety.

Design and synthesis of novel 3,4-dihydrocoumarins as potent and selective monoamine oxidase-B inhibitors with the neuroprotection against Parkinson's disease.

The monoamine oxidase-B (MAO-B) inhibitors with neuroprotective effects are better for Parkinson's disease (PD) treatment, due to the complicated pathogenesis of PD. To develop new hMAO-B inhibitors with neuroprotection, a novel series of 3,4-dihydrocoumarins was designed as selective and reversible hMAO-B inhibitors to treat PD. Most compounds showed potent and selective inhibition for hMAO-B over hMAO-A with IC values ranging from nanomolar to sub-nanomolar.

Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC values 0.85 μM and 0.

Val-Val-Tyr-Pro protects against non-alcoholic steatohepatitis in mice by modulating the gut microbiota and gut-liver axis activation.

Val-Val-Tyr-Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride-induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non-alcoholic steatohepatitis (NASH) have not been discovered.

Gramicidin-S-Inspired Cyclopeptidomimetics as Potent Membrane-Active Bactericidal Agents with Therapeutic Potential.

Antimicrobial peptides (AMPs) are promising antibacterial agents often hindered by their undesired hemolytic activity. Inspired by gramicidin S (GS), a well-known cyclodecapeptide, we synthesized a panel of antibacterial cyclopeptidomimetics using β,γ-diamino acids (β,γ-DiAAs). We observed that peptidomimetic CP-2 displays a bactericidal activity similar to that of GS while possessing lower side-effects.

Lycosquarrines A-R, Alkaloids from .

Eighteen new alkaloids, lycosquarrines A-R (-), and eight known alkaloids were isolated from the aerial parts of . Compounds - and , identified from natural sources for the first time, are uncommon lycopodine-type alkaloids with β-oriented H-4. Pentacyclic and represent the first examples of 5,12- and 5,11-epoxy alkaloids, respectively, and an epoxide-opening cyclization reaction is suggested to be a key step in their biosynthesis.

A trimeric tri-Tb including antimonotungstate and its Eu/Tb/Dy/Gd-codoped species with luminescence properties.

A trimeric tri-Tb3+-including antimonotungstate (AMT) hybrid Na17{(WO4)[Tb(H2O)(Ac)(B-α-SbW9O31(OH)2)]3}·50H2O (Tb3W28) was successfully synthesized, in which the capped tetrahedral {WO4} group plays a significant template role in directing the aggregation of three [B-α-SbW9O33]9- fragments and three Tb3+ ions. Eu3+/Tb3+/Dy3+/Gd3+-codoped AMT materials based on Tb3W28 were firstly prepared and their luminescence properties were investigated. The red emitter Eu3+, yellow emitter Dy3+, and nonluminous Gd3+ ions were codoped into Tb3W28 to substitute Tb3+ ions for investigating the energy transfer (ET) mechanism among Eu3+, Tb3+, and Dy3+ ions.

Design, synthesis and biological evaluation of rasagiline-clorgyline hybrids as novel dual inhibitors of monoamine oxidase-B and amyloid-β aggregation against Alzheimer's disease.

A series of rasagiline-clorgyline hybrids was designed, synthesized and investigated in vitro for their inhibition of monoamine oxidase and amyloid-β aggregation. Most of compounds were found to be selective and highly potent hMAO-B inhibitors showing IC values in the nanomolar, and exhibited a moderate inhibition of amyloid-β aggregation. 7-((5-(methyl(prop-2-yn-1-yl)amino) pentyl)oxy)chroman-4-one (6j) was the most interesting compound identified in this research, endowed with higher hMAO-B potency (IC = 4 nM) and selectivity (SI > 25000) compared to the reference selective inhibitor rasagiline (IC = 141 nM, SI > 355), and exhibited good inhibitory activity against Aβ aggregation (40.

Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities.

A series of novel coumarin-based N-hydroxycinnamamide derivatives were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds showed potent HDAC inhibitory activity and significant antiproliferative activity against human cancer cell lines MCF-7, HepG2, HeLa and HCT-116. Among them, compound 14f displayed the most potent HDAC inhibition, especially against HDAC1 with IC value of 0.

Intra-articular delivery of extracellular vesicles secreted by chondrogenic progenitor cells from MRL/MpJ superhealer mice enhances articular cartilage repair in a mouse injury model.

Background: Chondrogenic progenitor cells (CPCs) have high self-renewal capacity and chondrogenic potential. Intra-articular delivery of purified mesenchymal stem cells (MSCs) from MRL/MpJ "superhealer" mice increased bone volume during repair and prevents post-traumatic arthritis. Recently, although extracellular vesicles released from MSCs have been used widely for treating OA, the application of extracellular vesicles secreted by CPCs from MRL/MpJ mice in OA therapy has never been reported.

Double-Oxalate-Bridging Tetralanthanide Containing Divacant Lindqvist Isopolytungstates with an Energy Transfer Mechanism and Luminous Color Adjustablility Through Eu/Tb Codoping.

A double-oxalate-bridging tetra-Gd containing divacant Lindqvist dimeric isopolytungtate Na[Gd(CO)(HO)(OH)WO]·30HO () was obtained based on the reaction of NaWO·2HO, HCO, and GdCl in aqueous solution. Its dimeric polyoxoanion is established by two divacant Lindqvist [WO] segments connected by a rectangular tetra-nuclearity [Gd(CO)(HO)(OH)] cluster. Notably, neighboring trinuclear [NaO(HO)] clusters are interconnected to construct a picturesque 1-D sinusoidal Na-O cluster chain.

Design, synthesis and evaluation of novel ferulic acid derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease.

A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced β-amyloid (Aβ) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC, 19.

Design, synthesis and evaluation of quinolinone derivatives containing dithiocarbamate moiety as multifunctional AChE inhibitors for the treatment of Alzheimer's disease.

A series of novel quinolinone derivatives bearing dithiocarbamate moiety were designed and synthesised as multifunctional AChE inhibitors for the treatment of AD. Most of these compounds exhibited strong and clearly selective inhibition to AChE. Among them, compound was identified as the most potent inhibitor to both AChE and AChE (IC = 0.

Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-][1,4]oxazine derivatives as potent GPR 119 agonists.

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities.

Pristimerin attenuates cell proliferation of uveal melanoma cells by inhibiting insulin-like growth factor-1 receptor and its downstream pathways.

Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin-like growth factor-1 receptor (IGF-1R) is highly expressed in UM and has been shown to be associated with hepatic metastases. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells.