Increasing the selectivity and potency of a novel anthelmintic chemical entity

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Funding

  • National Research Network: Health and Life Sciences: £40,000.00

Funder Project Reference(s)

unknown
Effective start/end date01 Oct 201530 Sep 2018

Description

Schistosomiasis, caused by parasitic worms, is presently controlled by a single, sub-optimal chemotherapy, praziquantel (PZQ). With global mass drug administration (MDA) programmes distributing PZQ at an all time high, there are increased risks associated with PZQ failures and of development and spread of parasites tolerant or resistant to the only available anti-schistosomal chemotherapy. This represents a perilous situation in light of the World Health Organisation’s recently published goal of schistosomiasis elimination from selected countries throughout sub-Saharan Africa by 2020. We, therefore, aim to develop a combination or replacement chemotherapy, based on proprietary hit molecules, to improve treatment options for this neglected tropical disease causing the deaths of ~300,000 people per annum.

We propose a PhD project that progresses novel anthelmintics down the early-stage drug discovery pipeline. Our previous collaborative work with a Welsh-based company (Phytoquest Ltd.) has identified a preliminary ‘hit series’ of structurally defined, natural product analogues with diverse activity against human parasitic worms. Using these pre-existing data, we now will develop a cross-Wales interdisciplinary program that applies medicinal chemistry, computational biology and automated high content/high-throughput whole organism screens to schistosome blood flukes (causative agent of human and animal schistosomiasis).

To achieve this objective - identifying a selectively potent, anti-schistosomal compound with activity against both larvae and adult schistosome forms within three years - we will utilize an innovative screening approach in our drug discovery project. This approach is underpinned by our interdisciplinary expertise in medicinal chemistry, novel chemical entity synthesis, high-throughput in vitro whole organism assays, helminth biology and computational biology. As there are very few academic groups possessing the same collection of skills, our collaborative team is competitively positioned to competently train a PhD student proficient in these arts.