Transforming Higher Education for a Sustainable Tomorrow

A PhD studentship is available for three years for the following research project:

Title: Design and synthesis of aurones as potential neuroprotective agents
for Alzheimer’s disease

Acetylcholine is an important neurotransmitter in the central nervous system. It has been proposed that memory loss and intellectual deterioration associated with Alzheimer’s disease may in part be due to the loss of cholinergic neurons or activity in the brain. Research has been carried out on the use of anticholinesterases, agents that inhibit the enzyme that catalyses the hydrolysis of acetylcholine to augment brain cholinergic activity and thus alleviate the symptoms of Alzheimer’s disease. Two examples of such medicines currently used to treat Alzheimer’s disease are rivastigmine (Exelon) and donepezil (Aricept).

Borrowing structural features of these two established drugs, it is proposed that a new scaffold based on the naturally occurring flavonoid aurone be synthesized and evaluated as a potential anticholinesterase. The aurone template would be designed to incorporate structural features of donepezil and rivastigmine. A series of derivatives would be prepared and evaluated for cholinesterase inhibitory activity so that a comprehensive structure-activity relationship (SAR) profile can be canvassed. Promising compounds would be singled out for further evaluation of their pharmacokinetic properties. It is hypothesized that by combining the desirable features of the two drugs, an improved anticholinesterase agent may be uncovered while retaining the established pharmacokinetic profile (solubility, metabolic stability, blood-brain penetration) of the two drug molecules. Strategic inclusion of desirable structural features into a new scaffold may give rise to a multi-target agent that may have mechanism(s) of action in addition to its anticholinesterase activity, which may have an added advantage compared to existing Alzheimer drugs, an aspect that would be investigated on the promising compounds identified. A comprehensive SAR study would yield data regarding the necessary pharmacophores required in the aurone scaffold for anticholinesterase and neuroprotective properties and insights into how this new scaffold would interact with the cholinesterase enzyme to exert its effect (mode of action). Such data is important for the development of aurones as treatment for Alzheimer’s disease.

The student will gain skills in organic synthesis of small molecules, drug design, and in vitro biological assays and an overall training in medicinal chemistry.

Research will mainly be conducted at the School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang.

The successful student will receive monthly living allowances. He/she is encouraged to apply for research scholarships upon entry into the programme.

Requirements:
1. Malaysian student with a Chemistry/ Pharmacy/ Biotechnology/ Biomedical degree.
2. A good academic grade (CGPA 3.0 and above).
3. Prior lab experience in synthetic organic chemistry would be advantageous but not necessary.

Interested please contact:

Dr Lee Chong Yew
School of Pharmaceutical Sciences
Universiti Sains Malaysia
11800 Pulau Pinang.
Phone: 04-6532793
Email: chongyew@usm.my
Webpage: goodmolecules.blogspot.com

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