We investigated the effects of 1-amino-5-bromouracil on the benzodiazepine-γ-aminobutyric acid (GABA)A receptor complex to elucidate its central action. 1-Amino-5-bromouracil neither displaced nor enhanced [3H]muscimol, [35S] t-butylbi-cyclophosphorothionate (TBPS), or [3H]dehydroepiandrosteron...

Calcium-mediated signaling is crucial for the synaptic plasticity and long-term memory storage, which requires de novo protein synthesis. Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is an enzyme, which is involved in the maintenance of intracellular calcium homeostasis by converting inosito...

Inositol 1,4,5-trisphosphate 3-kinase (IP3K) catalyzes the ATP-dependent phosphorylation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] generating inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. The inhibitory effects of all possible 38 regioisomers of inositol phosphates [InsPn] on the IP3...

Fibroblasts from individuals with Down syndrome (DS; trisomy 21) exhibit increased inositol uptake. Here we examine the relationship between this increase in uptake and mass levels of free inositol and inositol 1,4,5-trisphosphate (IP3) in DS fibroblasts. We report that human fibroblasts contain...

d-myo-Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) analogues derived at 3-OH with a bulky substituent were chemically synthesized and structural features of vicinity surrounding the 3-OH of Ins(1,4,5)P3, recognized by metabolic enzymes and by the receptor were explored. 3-Benzoyl-, 3-methylbenzoy...

D-[35S(U)]mya-inositol 1,4,5-trisphosphorothioate ([35S]InsPS3), a synthetic, metabolically stable analogue of inositol 1,4,5-trisphosphate (InsP3) binds with high affinity (Ka 58.6±9.1 nM) to rat cerebellar revealing a high density of specific binding sites (Dmax 21.5±2.1 pmol/mg of protein)....

Frog skeletal muscle contains a kinase activity that phosphorylates inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate. The inositol 1,4,5-trisphosphate 3-kinase activity was mainly recovered in the soluble fraction, where it presented a marked dependency on free calcium concentr...

The synthesis of racemic 6-deoxy-6-hydroxymethyl scyllo-inositol 1,2,4-trisphosphate is described. This compound is a highly potent agonist at the platelet d-myo-inositol 1,4,5-trisphosphate receptor, and it binds to the rat cerebellar receptor with an affinity equal to that of the natural ligan...

Novel, structurally modified potential mimics of the second messenger d-myo-inositol 1,4,5-trisphosphate, based on the biologically active regioisomer d-myo-inositol 1,4,6-trisphosphate, were synthesised. dl-5-O-Benzyl-1,4,6-tri-O-p-methoxybenzyl-myo-inositol was the key intermediate for the pre...

Herein, we report the development of two fluorescent sensors for inositol 1,4,5-trisphosphate (InsP3), containing either two free cyclen or zinc(II)/cyclen groups preorganized into a binding cleft. Preorganization was achieved using a rigid acridine backbone, which was also exploited for fluores...

GluN2B subtype-selective NMDA antagonists represent promising therapeutic targets for the symptomatic treatment of multiple CNS pathologies. A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic moieties. Compounds were ev...

μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(...

A series of 23 N-(Pyridin-3-yl)benzamides was synthesized and evaluated for their potential to inhibit human steroid-11β-hydroxylase (CYP11B1) and human aldosterone synthase (CYP11B2). The most potent and selective CYP11B2 inhibitors (IC50 values 53–166 nM) were further evaluated for their pot...

From hit compounds identified by high throughput screening (HTS), we have found compound 1 as a lead TRPV1 antagonist and confirmed its potential as a treatment for pain. Compound 1 has led to potent TRPV1 antagonistic benzamide derivatives ((±)-2: human IC50 = 23 nM, (±)-3: human IC50 = 14 nM...

Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedg...

A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target com...

In the present study, a series of m-(4-morpholinoquinazolin-2-yl)benzamides were designed, synthesized and characterized. The antiproliferative activities of the synthesized compounds were evaluated against two human cell lines (HCT-116 and MCF-7). Compounds with IC50 values below 4 μM were fur...

In the present study, a series of m-(4-morpholino-1,3,5-triazin-2-yl)benzamides were designed, synthesized and characterized. Their antiproliferative activities against HCT-116 cell and MCF-7 cell at 10 μM were evaluated by MTT assay. Compounds T6, T10, T11, T12 and T19 exhibited potent antipro...

The crystal and molecular structure of 2-amino-3-benzyloxy pyridinium picrate (ABPP) have been elucidated using spectroscopic (MS, NMR and FTIR) and single crystal X-ray diffraction. In ABPP, the piperidene and phenyl ring are perpendicular to each other and intramolecular hydrogen bonds (N2⋯H2B...

In this work we describe a simple and efficient general methodology for 2-arylbenzothiazole preparation employing disulfides and carboxylic acids. The reaction is promoted by tributylphosphine that acts both in disulfide bond cleavage and as activating agent for coupling with carboxylic acids. T...