Design of novel inhibitors of trypanosomatid parasites
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Neglected tropical diseases (NTDs) are a group of infectious diseases that are endemic in tropical and subtropical regions. The associated infectious agents include protozoa, bacteria, viruses, and helminth parasites. In particular, Human African Trypanosomiasis, Chagas disease and Leishmaniasis are responsible for high mortality and morbidity rates in developing countries. However, the current treatments for trypanosomiasis and leishmaniasis have severe side effects and can be lethal. Most of these treatments are antiquated, resulting in emerging drug resistance, and are difficult to administer (mostly by injection). Therefore, there is an urgent demand to find safer, cheaper, and more efficient alternatives to the existing drugs. Natural products play an important part in drug discovery, with more than 50 % of modern drugs being directly or indirectly derived from them. In particular, the natural product chamuvarinin was found to have potent activity against trypanosomatid parasites. In this project, we synthesized a series of chamuvarinin based analogues, aiming to expand the library of trypanosomatid inhibitors, and further exploring the structure-activity relationship (SAR).
Thesis, MPhil Master of Philosophy
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