Synthesising theraputic compounds for dementia and Alzheimer’s Disease

This project aims to chemically synthesise compounds that destabilise and deconstruct the β-amyloid oligomer molecular-environment that facilitates β-amyloid gain in neurotoxic function.

Project dates: This chemical-medicinal synthesis project commenced 2013 and is ongoing.

Grants and funding: ARC DP Grant submitted; miscellaneous research funds.

Every four seconds there is a new case of dementia in the world. There are 7.7 million new cases of dementia each year and the global cost of Alzheimer's Disease (AD) and dementia is estimated to be $604 billion. The alarmingly increasing incidence of AD worldwide is paralleled by the search for compounds with neuroprotective activity, a search that has intensified in recent years.

AD is a multifactorial disease, correlated with neuronal damage in different brain areas and is still incurable. Because of this, protection of neuronal cells by anti-amyloidogenic substances or the retardation of amyloid fibril formation is of high priority and an actively pursued therapeutic concept.

This project is driven by the efforts and enthusiasm of RMIT scientists and postgraduate students who realise there can be no health without mental health. It is their objective to synthesise green tea inspired compounds against AD as a cost effective and accessible therapy option.

Description

Generation of scaffolds to prevent brain β-amyloid misfolding and aggregation.

Research strategy

Natural green tea product epigallocatechingallate [EGCG] inspired analogues/scaffolds can be produced from intermediates utilised in total synthesis that are not easily accessed from green tea biosynthesis.

Why chemical synthesis? 

Natural products such as EGCG target proteins with a high number of protein-protein functional interactions (high biological network connectivity) and that these protein targets have higher network connectivity than disease genes. This suggests that modified EGCG or novel small molecules will be required to discover drugs targeting the root causes of dementia disease in the future.

Key people

  • Associate Professor Helmut Hügel, Project Leader
  • Professor Ewan Blanch, Research Collaborator
  • Professor Andrew Smith, Research Collaborator
  • Dr Neale Jackson, Research Associate

Publications

  • H.M. Hügel, N. Jackson, B.H. May, C.C.I. Xue, Chinese Herbs for Dementia Diseases, Mini Reviews in Medicinal Chemistry, 2012, 12, 371-379.
  • H.M. Hügel, N. Jackson. Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases, Mini Reviews in Medicinal Chemistry, 2012, 12, 380-387.
  • Brian H. May, Chuanjian Lu, Louise Bennett, Helmut Hügel, Charlie C. L. Xue, Evaluating the traditional Chinese literature for herbal formulae and individual herbs used for memory disorders, Biogerontology, 2012, 13, 299-312.
  • Benjamin L. Alford and Helmut M. Hügel, Total synthesis of (+) Pentamethylsalvianolic acid C, Org. Biomol. Chem. 2013, 11, 2724-2727.
  • Hügel, H.M. and Jackson, N. Herbs and Dementia: a focus on Chinese and other traditional herbs, Diet and Nutrition in Dementia and Cognitive Decline, Martin, C. and Preedy, V. (eds.), Elsevier Academic Press, 2014 ISBN: 978-0-12-407824.
  • Hügel, H.M. and Jackson, N. Danshen Diversity Defeating Dementia, Bioorg. Med. Chem. Lett. 2014, 24, 708-716.
  • Hügel, H.M. Brain food for AD-free ageing: Focus on Herbal medicines, Natural compounds as therapeutic agents for amyloidogenic diseases, Advances in Experimental Medicine and Biology Book Series, Springer-Verlag. N. Vassallo (ed.) 2015.
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Acknowledgement of country

RMIT University acknowledges the people of the Woi wurrung and Boon wurrung language groups of the eastern Kulin Nations on whose unceded lands we conduct the business of the University. RMIT University respectfully acknowledges their Ancestors and Elders, past and present. RMIT also acknowledges the Traditional Custodians and their Ancestors of the lands and waters across Australia where we conduct our business.