Abstract:
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive,
functional, and behavioural alterations. AD is age-related and causes substantial
structural and functional damage to the brain resulting in severe cognitive dysfunction.
World Health Organization (WHO) estimated that by 2050, one in every 85 people in
the world would be living with AD. Medications that will improve cognition or
ameliorate neuropsychiatric symptoms of patient in the symptomatic phase of AD are
needed to improve memory and behaviour. However, current treatment strategies for
this disease is still in its infancy and fails to delay the progression of the disease. The
new approach of multi-target directed ligands (MTDLs) has been adopted recently,
which involves targeting multiple enzymes simultaneously with a single molecule.
The research work presented in the thesis is divided into three parts. The first part deals
with de novo fragment growing strategy for the design of novel 3,5-diarylpyrazoles and
hit optimization of spiropyrazoline derivatives as acetyl cholinesterase inhibitors. The
second series includes a library of 2-substituted benzo[d]oxazol-5-amine derivatives,
designed by using the scaffold hopping guided MTDLs strategy. The designed
compounds were synthesized and evaluated through various in-vitro and in-vivo
biological studies. The neurobehavioral studies in rats were performed to assess the
effect of compounds in improving the learning and memory. The third part involves the
establishment of multi-modal approach with ChEs, NMDAR antagonism, Aβ
aggregation and neurotoxicity. Wherein, we investigated novel triazole bridged
cycloaryl hybrids. The study led to the publication of two research papers.
