Synthesis and biological evaluations of NO-donating oxa- and aza-pentacycloundecane derivatives as potential neuroprotective candidates
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Date
2018
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
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.
Description
Keywords
NO-donating, S-nitrosylation, Neuroprotection, Polycyclic cage, Calcium influx
Citation
Sharma, R. et al. (2018). Synthesis and biological evaluations of NO-donating oxa- and aza-pentacycloundecane derivatives as potential neuroprotective candidates. Molecules, 23: 308