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• 2958-72-7 Cookson's diketone 
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• 62-23-7 4-nitro-benzoic acid 

Relevant academic research and scientific papers

Synthesis and Biological evaluations of NO-donating Oxa- and Aza-pentacycloundecane derivatives as potential neuroprotective candidates

In order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds were done for cytotoxicity, neuroprotective abilities, the inhibition of N-methyl-D-aspartate (NMDA)-mediated Ca2+ influx, the inhibition of voltage-mediated Ca2+ influx, and S-nitrosylation abilities. All of the compounds showed low toxicity. With a few exceptions, most of the compounds displayed good neuroprotection and showed inhibitory activity for NMDA-mediated and voltage-gated calcium influx, ranging from high (>70%) to low (20-39%) inhibition. In the S-nitrosylation assay, the compounds with the nitro moiety as the NO-donating group exhibited low to good nitrosylation potency compared to the positive controls. From the biological evaluation of the tested compounds, it was not possible to obtain a simple correlation that could explain the results across all of the biological study domains. This can be ascribed to the independent processes evaluated in the different assays, which reiterate that neuroprotection is a result of multifactorial biochemical mechanisms and interactions. However, these results signify the important aspects of the pentacylcoundecylamine neuroprotectants across different biological study realms.

S-nitrosylation and attenuation of excessive calcium flux by pentacycloundecane derivatives

A novel series of polycyclic amines, containing nitrogen monoxide donating moieties, were synthesised and tested for calcium channel and N-methyl-D-aspartate receptor modulating activity. The synthesised compounds were classified into two groups, based on their nitrogen monoxide donating moieties: unsaturated nitro compounds (1, 2 and 3) and nitro esters, or nitrates (4, 5 and 6). The nitrates were obtained via the reaction of hydroxyl functionalities with thionylchloride nitrate. All of the compounds synthesised exhibited significant (p 0.01) S-nitrosylation capacity. The calcium channel activity of the polycyclic amines was evaluated using a KCl mediated fluorescent calcium flux assay. All the compounds exhibited better calcium channel antagonism than the lead structure, NGP1-01, with compound 1 exhibiting calcium channel blockade comparable to the commercially available nimodipine at concentrations of 10 μM and 1 μM. Compounds 3 and 4 inhibited calcium flux to these levels at 10 μM concentrations. NMDA/glycine mediated N-methyl-Daspartate receptor (NMDAR) calcium influx inhibition was evaluated at a 100 μM concentration using a fluorescent calcium flux assay. All the compounds exhibited NMDAR antagonism with compounds 1 (25.4 %), 2 (20.24 %), 3 (33.14 %) and 6 (24.55 %) showing the most significant NMDAR inhibitory activity (p 0.01). No clear correlation was observed between the S-nitrosylation capabilities of the compounds and their calcium channel activity or NMDAR channel antagonism, indicating that other factors probably play a more decisive role in the mechanism of pentacycloundecylamine channel modulation. This could include the geometric and steric bulk considerations that have been described to contribute to the channel activities of the pentacycloundecylamines. All the compounds synthesised exhibited promising calcium channel and NMDAR channel inhibitory activity and show promise as potential lead compounds for drug development against neurodegeneration.