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Natural Product-Inspired Therapies for Leishmaniasis and Chagas Disease

Objective

The development of new therapies for leishmaniases (which affeThe development of new therapies for visceral leishmaniasis (affects ~12 million people worldwide) and Chagas disease (~6-7 million people worldwide) is critically dependent on the identification of novel pharmacophores with new modes of action. Current treatments suffer from severe side effects, high cost, patient compliance issues, and emerging resistance; as such, new therapeutic leads are urgently required. Despite significant investment, limited progress has been made with research into new 'synthetic' drugs: no candidates are in clinical trials (although two compounds have recently progressed to preclinical evaluation for VL). In contrast, research into natural product-derived drugs has been largely ignored, despite their track record as frontline treatments for VL (amphotericin B) and the most prominent parasitic disease, malaria (artemisinin). In this project, we challenge this dogma through the exploration of a series of structurally-related alkaloid natural product families, where highly promising antiparasitic bioactivity has been observed in the few examples studied. The selection of these families is additionally based on their accessibility through concise, modular and convergent synthetic strategies, which facilitate modification. We couple this central focus of synthetic chemistry with collaborations to evaluate bioactivity (with expert parasitologist Prof Andre Tempone), and identify pharmacokinetic/dynamic limitations (with expert pharmacologist Prof Kevin Read), thereby informing analogue refinement and synthesis. This multidisciplinary approach will greatly enhance the impact of the synthetic chemistry work by providing 'real-time' feedback into compound design, enhancing project efficiency and progress. Our overarching, long term impact objective is to identify a new pharmacophore (and potentially new parasite target / mode of action) for the potential development of VL/CD therapies.

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 933,76
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 933,76
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