Additional information supporting the academic profile of Professor Paul Kong. All number references below refer to publications listed on the main profile page.

 

Research Interests (cont.)

Anti-cancer, anti-parasitic and antioxidant therapeutics

For a number of years, the focus of my research has been in the design and synthesis of analogues/homologues/derivatives of natural polyamines. The presence of polyamines is essential for the proliferation of all eukaryotic cells. This has generated intense interests in the chemistry and biology of polyamines with potential applications in the development of novel therapeutic agents [1]. We were first to design and synthesise two new families of compounds called the ‘Oxa-polyamines and Bisnaphthalimidopropyl polyamines’, BNIPs [2, 3]

Oxa-polyamines and Bisnaphthalimidopropyl polyamines

These compounds can potentially be used as tools to elucidate the precise role of polyamines in cells proliferation and metabolism. Furthermore they have shown very good in vitro activity against a panel of human cancer cells [4, 5, 6]. For the first time we reported that the ‘Bisnaphthalimidopropyl polyamines’ (i) strongly bind to DNA (ii) inflict DNA damage and affect DNA repair at low drug concentration in cancer cells (iii) causes cell death by the process of apoptosis (programmed cell death) (iv) facilitate drug delivery using an active transport system [7, 8]. A second generation of the ‘Bisnahpthalimidopropyl polyamines’ demonstrated enhanced in vitro and in vivo activity against colon cancer cells and parasite Leishmania infantum [9, 10, 11, 12, 13] and this had led a patent application [14].

Colon cancer cells

However the precise mode of action of this group of compound still remains unclear. One of the possible targets we envisage is the Histone deaceylase (HDAC) enzymes. Histone acetylation has been associated to gene-specific activation by transcription factors. It plays a vital role to cell cycle control and has been linked to the uncontrolled cell proliferation. Furthermore HDAC also modulate the expression of tumour suppressor p53. Therefore Histone deacetylases (HDACs) and their inhibitors are a promising class of new anticancer drugs. Indeed investigations (in collaboration with the University of Porto) on a Leishmania HDAC that belongs to the Class III deacetylase enzymes (LiSIR2RP1) had led us in the discovery of bisnaphthalimidopropyl (BNIP) derivatives as a new class of HDAC inhibitors [12, 13].

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Drug formulation development

Poorly water-soluble drugs present a major challenge to the pharmaceutical industry as it may hinder or even prevent the progress of the drug into clinical use. We have shown that the use of nano-sized delivery systems based on 'grafted' polyallylamine (PAA) was able to significantly enhance the aqueous solubility of many hydrophobic drugs including our BNIP lead compound [15, 16]. The latter formulation achieved comparable in vivo anti-tumoural activity compared to Gemcitabine [17].

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Bioactive compounds from natural sources

Other aspects of my research entail the isolation and identification of novel compounds from plants materials and to study their biological activities and potential applications [18, 19, 20, 21] 

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