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Drug
Hong Kong has not been known as a centre for new drug development, but that may be about to change. Projects underway at HKU are expected to advance the University’s prominence in the field and offer new treatments for patients.
Scholars from the Faculty of Science and the Li Ka Shing Faculty of Medicine are collaborating to investigate and record new compounds that could lead to drug discoveries.
They already have a strong track record in designing and synthesising natural compounds and metallodrug leads, and are continuing to make advances in this field. Attention is also turning to traditional Chinese medicines (TCMs) because while these have been successfully used for many centuries, little is known about how they work.
Researchers hope to unravel some of the mysteries of TCMs and other drug leads using molecular docking experiments and genomic, proteomic and other technologies to support their work.
"We have established a platform to facilitate this research and now we want to demonstrate that it is feasible to develop new drugs in Hong Kong," said Professor C.M. Che of the Department of Chemistry and convenor of the Drug theme.
Traditional Chinese medicines
TCMs appear to be effective against a wide range of diseases and researchers are keen to know why. One focus at HKU is on saponins, a class of compounds present in many TCMs. Three strands of research are underway: the active mechanisms in saponins (see Drug Development, below), how TCMs work against specific diseases and quality control.
One of the most promising leads is coptis (huanglian), which is used to treat inflammatory diseases. Our researchers have isolated berberine as a major active component and found it may inhibit migration of nasopharyngeal cancer cells (the sixth most common cancer in Hong Kong).
They have also shown that water extract of coptis offers remarkable liver protection in animal models. Liver cancer is the third most common cancer in Hong Kong and has a high death rate. "The next stage is to standardise this treatment into a form that could be used clinically and elucidate its precise anti-tumour effects," Dr Y. Feng of the School of Chinese Medicine said.
Another interesting lead is oxyresveratrol. This is found in natural foods such as mulberries and is a relation of resveratrol, an anti-oxidant found in red wine that can be potentially toxic to neurons if the dose is inappropriate. HKU researchers recently discovered that oxyresveratrol provided a wider effective dosage of neuroprotection than resveratrol, and will evaluate its use in treating Parkinson’s Disease.
Finally, while TCMs offer opportunities for drug discovery, it is important to secure a quality source of these medicines. Technology normally used to analyse agrochemicals such as herbicides is being deployed in an unusual approach to profile saponin-rich medicinal plants.
"The information should help to differentiate raw herbs collected from different geographic locations and be an important tool in the quality control and modernisation of TCMs," said Dr K.M. Ng of the Department of Chemistry.
Drug development
Crucial to drug discovery is the creation of unique compound libraries of potential drug leads. These provide information on the chemical structure-activity relationship and on compounds that could be screened to test their effectiveness against a wide variety of diseases and determine their potential for drug development.
The saponins found in TCMs are a focus here. They have shown a broad spectrum of interesting properties, such as anti-inflammatory, anti-fungal, antibacterial, anti-viral and anti-cancer. Yet very few have been studied clinically to understand their action mechanisms in depth.
Researchers at HKU are pursuing sophisticated studies of the action mechanisms of saponins and metallodrugs, using proteomics, molecular and genetic technologies.
"So far we have discovered a class of saponins that induces autophagy, in which cells consume and recycle themselves," Professor Che said. "This could be useful in treating several diseases such as cancer, Alzheimer’s and Huntington’s. We have also discovered cytotoxic gold drugs, which are 100 times more potent than the clinically used cisplatin for the treatment of terminal cancers."
Further experiments will be carried out to verify the potential molecular targets of saponins and cytotoxic gold drugs. The hope is that these studies will provide a basis for designing and synthesising new drug leads that enhance therapeutic properties and reduce side effects.
