As part of a continuing study of the synthesis and chemistry of new, substituted pentacyclo(5.4.0.0²，⁶.0³，¹º.0⁵，⁹)undecanes, the following compounds have been synthesized: 1: X=O, Y=SiMe_3; 2: X=CH_2, Y=SiMe_3; 3: X=O, Y=Cl; 6: X=OAc, Y=H; 8: X=OC(O)Ph, Y=H; 9: X=OSO_2Ph, Y=H; 11: X=OH, Y=H; 12: X=OMe, Y=H; 14: X=CHSiMe_3, Y=SiMe_3; 15: X=OH, Y=Cl; 16: X=OAc, Y=Cl; 17: X=OMe, Y=Cl. An important objective of this work is to prepare new polycyclic cage compounds which can be utilized as intermediates for the synthesis of new, substituted tricyclopentanoid natural products (triquinanes) and related systems. Compounds 1-4 were identified as target molecules in this connection.

Magister Pharmaceuticae - MPharm / Recent scientific findings have highlighted the beneficial roles of polycyclic cage compounds in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Further interest into the chemistry of these compounds is stimulated by their remarkable ability to improve the pharmacokinetics profile of known neuroprotective agents. As potent lipophilic scaffolds, they can be employed to target the brain delivery of desired compounds. Inflammation is a key mediator of neuronal cell's degeneration as activated microglia and other inflammatory mediators propagate oxidative damage and neuronal loss. Epidemiological and clinical evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) slow down the progression and onset of neurodegenerative diseases. The beneficial effects of NSAIDs in ND can be attributed to their ability to inhibit cyclooxygenase enzymes thereby halting the biosynthesis of prostaglandins (PG) which are powerful mediators of inflammation. NSAIDs also inhibit the expression of pro- inflammatory genes. Despite their potential neuroprotective activity, NSAIDs are poorly lipophilic due to the presence of polar carboxylic acid groups and will therefore ionise at physiological pH, deterring them from reaching the desired site of action in the central nervous system (CNS).

Doctor Pharmaceuticae - Dpharm / Among neurological disorders, many of the most devastating disorders are neurodegenerative. Modern research associates excitotoxicity to a variety of neuropathological conditions, suggesting that the neurodegenerative diseases with distinct etiologies may have excitotoxicity as a common pathway. Excitotoxicity occurs through over-stimulation of receptors for excitatory neurotransmitters like the N-methyl-D-aspartate (NMDA) receptors. Due to the relevance of NMDA receptors and excitotoxic processes, the antagonism or modulation of NMDA receptors is used as a therapeutic tool against neurodegenerative diseases. NMDA receptor activity can be modulated by S-nitrosylation and this modulation of NMDA receptor activity can be utilised in the development of neuroprotective drugs.

>Magister Scientiae - MSc / This study focused on the synthesis of a series of novel tricycloundecane derivatives and evaluation of these compounds for neuroprotection using the fluorescent ratiometric calcium assay that indicates the ability of the test compounds to inhibit NMDA receptors and VGCC. The cycloaddition reaction between p-benzoquinone and monomerised dicyclopentadiene yielded tricycloundeca- 4,9-diene-3,6-dione which was used as the base structure and further derivatised. These derivatives were conjugated with benzylamine to form a series of imines and amines. A total of 10 compounds were synthesised for evaluation of inhibition of calcium influx through NMDA receptor channels and voltage-gated calcium channels. The structures were confirmed using NMR, IR and MS. On the proton NMR, the characteristic AB-quartet system was observed in the region of 1-2 ppm for all the compounds and the aromatic moiety was observed between 6.5-7.5 ppm for the novel polycyclic amines. These, with other functional groups, were used to confirm the individual structures