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Calcineurin, the predominant Ca2+/calmodulin-dependent serine/threonine protein phosphatase (also known as protein phosphatase 2B), is highly expressed in immune T cells and the nervous system, including the dorsal root ganglion and spinal cord. It controls synaptic transmission and plasticity by maintaining the appropriate phosphorylation status of many ion channels present at presynaptic and postsynaptic sites. As such, normal calcineurin activity in neurons and synapses is mainly involved in negative feedback regulation in response to increased neuronal activity and intracellular Ca2+ levels. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) are widely used as immunosuppressants in tissue and organ transplantation recipients and for treating autoimmune diseases but can cause severe pain in some patients. Furthermore, diminished calcineurin activity at the spinal cord level may play a major role in the transition from acute to chronic neuropathic pain after nerve injury. Restoring calcineurin activity at the spinal cord level produces long-lasting pain relief in animal models of neuropathic pain. In this article, we provide an overview of recent studies on the critical roles of calcineurin in regulating glutamate NMDA and AMPA receptors, voltage-gated Ca2+ channels, potassium channels, and transient receptor potential channels expressed in the spinal dorsal horn and primary sensory neurons. [ABSTRACT FROM AUTHOR]

A new series of 4-azasteroidal-20-oxime derivatives have been synthesised from progesterone. All the new compounds have been characterised by analysis and spectroscopic data and subsequently evaluated for their anticancer activity in vitro against T24 cell. The studies show that the methyl and ethyl oxime-ethers exhibited higher activity than the aryl substituted oxime-esters. [ABSTRACT FROM AUTHOR]

The synthesis of novel trispiropyrrolidine derivatives has been achieved by a one-pot, three-component 1,3-dipolar cycloaddition reaction of 3-aryl-5-arylmethylenespiro[indole-3′,2-[1,3]thiazolane]-2′(1H),4-dione, isatin and sarcosine in refluxing toluene which produced the corresponding cycloadducts in good yields. The structures were determined by 1 H NMR, IR and elementary analysis. [ABSTRACT FROM AUTHOR]

3,3,17,17-Diethylenedioxyandrost-5-ene was obtained by ketalisation of androstenedione, which was oxidised with PDC and t-BuOOH to form 3,3,17,17-diethylene-dioxyandrost-5-ene-7-one. Stereoselective reduction of 3,3,17,17-diethylene-dioxyandrost-5-ene-7-one by NaBH4 in the presence of CeCl3 .6H2 O gave 3,3,17,17-diethylenedioxy 7β-hydroxy-androst-5-ene, which was deprotected with p-toluenesulfonic acid to gave 3,3-ethylenedioxyandrost-5-ene-7β-hydroxy and androst-4,6-dien-3,17-dione. A series of androstenedione derivatives were obtained from 3,3-ethylenedioxyandrost-5-ene-7β-hydroxy by the esterification reaction. Their structures were confirmed by MS,1 H NMR, 13C NMR and HRMS. [ABSTRACT FROM AUTHOR]

A simple and efficient method has been developed for stereoselective one-pot synthesis of (E)-3-(4-arylpiperazin-1-yl)-1-arylprop-2-en-1-ones by condensation of aryl ketones with arylpiperazines and N, N-dimethylformamide dimethyl acetal in acetic acid with 54-69% yields. Compared with reported methods, this one-step procedure appears to be a useful approach to prepare (E)-β-enaminoketones with good stereoselectivity, simple operation and moderate yields. [ABSTRACT FROM AUTHOR]