Over the past decade, two independent technologies have emerged and been widely adopted by neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin other opsins, chemogenetics G protein-coupled receptors (Designer Receptors Exclusively Activated Designer Drugs (DREADDs)) orthologous ligand-receptor pairs. Using directed molecular evolution, types of DREADDs derived from human muscarinic acetylcholine developed: hM3Dq activates...

ABSTRACT The antiviral efficacies and cytotoxicities of 2′,3′- 4′-substituted 2′,3′-didehydro-2′,3′-dideoxycytidine analogs were evaluated. All compounds tested (i) against a wild-type human immunodeficiency virus type 1 (HIV-1) isolate (strain xxBRU) lamivudine-resistant HIV-1 isolates, (ii) for their abilities to inhibit hepatitis B (HBV) production in the inducible HepAD38 cell line, (iii) bovine viral diarrhea (BVDV) acutely infected Madin-Darby kidney cells. Some demonstrated potent...

The Janus kinase (JAK) family comprises four members (JAK1, JAK2, JAK3, and Tyk2) that play a key role in mediating cytokine receptor signaling. JAK inhibition thus modulates cytokine-mediated effects. In particular, selective of JAK1 or JAK3 may provide an efficient therapeutic agent for the treatment inflammatory diseases, with minimized side this study, as part our continued efforts to develop inhibitor, series 1,2-disubstituted benzimidazole-5-carboxamide derivatives was prepared their...

To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole benzoxazole derivatives with indole moiety were designed synthesized. Most the synthesized compounds showed inhibitory activities against selectivity over MAO-A. The most active compound was 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole an IC50 value 28 nM no apparent effect on MAO-A activity at 10 μM. Based reversibility assay, 5b turned out to be fully 95%...

Quercetin-amino acid conjugates with alanine or glutamic moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects evaluated. A quercetin-glutamic conjugate, 7-O-Glu-Q (3a), was as potent verapamil in reversing MDR sensitized MES-SA/Dx5 cells to various anticancer drugs EC50 values 0.8-0.9 μM. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug efflux by Pgp, Pgp ATPase assay showed interacts the drug-binding...

Abstract Parkinson's disease (PD) is a progressive neurodegenerative caused by loss of dopaminergic neurons in the substantia nigra. Monoamine oxidase‐B (MAO‐B) inhibition promising strategy for modification. Here, we synthesized series 2,6‐diarylbenzo[ d ]oxazoles and identified two potent selective hMAO‐B inhibitors: 4,4′‐(benzo[ ]oxazole‐2,6‐diyl)diphenol 4a (IC 50 = 0.182 μM) 4‐(2‐(3‐fluorophenyl)benzo[ ]oxazol‐6‐yl)phenol 4f 0.184 μM). Molecular modeling indicated that benzoxazole core...

Exocyclic products having cis-2,5 and cis-2,6 substitution were synthesized from terminally substituted alkynyl alcohols with various aldehydes via Prins-type cyclization in good yields. It is of interest that 5- 6-exocyclic vinyl cations generated as a result could be trapped triflate CH2Cl2 to give 3-furanylidenes 3-pyranylidenes. Those 3-pyranylidenes underwent hydrolysis the corresponding 3-acyl-substituted all-cis-configured isomers, such 2,3,5-trisubstituted tetrahydrofurans...

In order to increase stability of quercetin, its metabolically and chemically susceptible hydroxyl groups 7-OH 3-OH respectively were transiently blocked with a pivaloxymethyl (POM) promoiety provide two novel quercetin conjugates [7-O-POM-Q (2), 3-O-POM-Q (3)]. the absence stabilizer (ascorbic acid), synthesized showed significantly increased in cell culture media [t1/2 = 4 h 52 (3)] compared (t1/2 < 30 min) prodrug 1 0.8 h). addition, conjugate 2 underwent efficient cellular uptake...

Serotonin (5-hydroxytryptamine, 5-HT) levels are increased by light exposure but the role and mechanism of 5-HT in pigmentation skin cells unclear.To clarify effect on melanogenesis to determine receptor subtype involved.B16F10, SK-MEL-2 Melan-A were cultured Dulbecco's modified Eagle's medium with low fetal bovine serum. The three cell lines treated various concentrations 5-HT, agonists antagonists. involvement 2A (5-HTR2A) was examined gene silencing use 5-HTR2A antagonists.5-HT agonist,...

In recent years, there has been growing interest in the near-infrared (NIR) fluorescence imaging of tau fibrils for early diagnosis Alzheimer's disease (AD).

A series of aryloxazole, thiazole, and isoxazole derivatives was synthesized as vascular-targeting anticancer agents. Antiproliferative activity tumor vascular-disrupting all the compounds were tested in vitro using various human cancer cell lines HUVECs (human umbilical vein endothelial cells). Several with an arylpiperazinyl oxazole core showed excellent cytotoxicity metabolic stability vitro. Among this series, two representative (6-48 6-51) selected for evaluation effects vivo...

Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression Alzheimer's disease (AD) because its proven correlation with degree cognitive impairment AD patients. Accordingly, noninvasive imaging tau aggregates been highlighted promising diagnostic tool for AD. We have previously identified tau-specific "turn-on" near-infrared fluorescent (NIRF) probe (1), and, this study, structural modification was performed to optimize...

Development of a novel, tau-selective smart near-infrared fluorescence (NIRF) probe was attempted by combining the previously identified core scaffold 3,5-dimethoxy-N,N-dimethylaniline-4-yl moiety, with characteristic donor-π-acceptor architecture NIRF Aβ probes DANIR-2c and MCAAD-3. A series compounds (2 3) were prepared, which as "turn-on" for visual detection tau aggregates fibrils (λem = 650 nm, Stokes shifts 70–110 nm). In particular, combination 3,5-dimethoxy-N,N-dimethylanilin-4-yl...

Enantiomeric synthesis of d- and l-cyclopentenyl nucleosides their antiviral activity against HIV West Nile virus are described. The key intermediate (−)- (+)-cyclopentenyl alcohols (7 15) were prepared from d-γ-ribonolactone d-ribose, respectively. Coupling 7 with appropriately blocked purine pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded target l-(+)-cyclopentenyl (24-28, 31, 33, 36). d-(−)-Cyclopentenyl (1, 40, 43, 52−56) also a similar procedure for...

Among the various methane activation reactions, oleum-mediated (SO3–H2SO4) oxidation to methyl bisulfate (MBS), a methanol precursor, is one of best methods in terms conversion and product selectivity. In this report, we investigated effect catalyst concentration on MBS yield using systems (bpym)PtCl2, K2PtCl4, (DMSO)2PtCl2 at 180 °C for 3 h. (bpym)PtCl2 showed very high stability as well over 84%, but its catalytic activity expressed turnovers h was range 50–500. K2PtCl4 17 000 low...

The recent outbreak of severe acute respiratory syndrome (SARS), which is an illness, caused by newly discovered SARS coronavirus (SARS-CoV). Herein we describe the antiviral activity several classes nucleoside analogues evaluated against SARS-CoV in Vero 76 cells, some exhibited moderate activity.

Serotonin 5-HT6 receptor antagonists are thought to play an important role in the treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel potent provide a new idea for drug design, we used ligand-based pharmacophore perform virtual screening commercially available database. A three-dimensional common feature model was developed by using HipHop program provided Catalyst software as query recursive partitioning (RP) which can separate active inactive compounds...