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Coles Chagas disease. Discovery of a TcGlcK inhibitor through lead optimisation of CBZ-GlcN at Bayshore Shopping Centre in Ottawa, ON
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Seminar paper from the year 2023 in the subject Medicine - Pharmacology, Pharmacy, grade: A+, Utrecht University, course: Medicinal Chemistry, language: English, abstract: Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease that poses a serious threat to public health in South and Central America, but not only there. The disease affects large groups of people in underdeveloped areas, causing around 12,000 deaths every year. There is no effective treatment for the chronic phase of the disease, while the drug-resistant strains of the Trypanosoma cruzi parasite start challenging the usefulness of the acute phase treatment. Consequently, new drug candidates need to be developed. This paper proposes a novel drug candidate that was created by optimising the lead molecule called CBZ-GlcN. The affinity of the reported drug candidate is exceptional (Kdiss = 7.11 nM), showing a 890-fold improvement over the affinity of CBZ-GlcN for TcGlcK. Furthermore, the new molecule exhibits advantageous pharmacokinetic properties. The paper also reports a suggested synthesis route for the drug candidate, which can be used to perform in vivo tests examining properties such as affinity, specificity, and toxicity of the drug candidate.
Seminar paper from the year 2023 in the subject Medicine - Pharmacology, Pharmacy, grade: A+, Utrecht University, course: Medicinal Chemistry, language: English, abstract: Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease that poses a serious threat to public health in South and Central America, but not only there. The disease affects large groups of people in underdeveloped areas, causing around 12,000 deaths every year. There is no effective treatment for the chronic phase of the disease, while the drug-resistant strains of the Trypanosoma cruzi parasite start challenging the usefulness of the acute phase treatment. Consequently, new drug candidates need to be developed. This paper proposes a novel drug candidate that was created by optimising the lead molecule called CBZ-GlcN. The affinity of the reported drug candidate is exceptional (Kdiss = 7.11 nM), showing a 890-fold improvement over the affinity of CBZ-GlcN for TcGlcK. Furthermore, the new molecule exhibits advantageous pharmacokinetic properties. The paper also reports a suggested synthesis route for the drug candidate, which can be used to perform in vivo tests examining properties such as affinity, specificity, and toxicity of the drug candidate.
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