H2020Индивидуална стипендия2019–2021

NPsVLCD · Natural Product-Inspired Therapies for Leishmaniasis and Chagas Disease

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-08-01 → 2021-07-31
Финансиране от ЕС: 212 934 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Природни съединения се изследват като основа за нови лекарства срещу паразитите, причиняващи леишманиоза и болест на Чагас. Това е важно, защото тези заболявания засягат милиони хора по света и често са фатални, ако не се лекуват.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Natural Product-Inspired Therapies for Leishmaniasis and Chagas Disease

This MSC Action is titled “Natural Product-Inspired Therapies for Leishmaniasis and Chagas Disease”. This project aims to: (1) explore the potential of natural products, selected based on promising bioactivities, to serve as new templates for the development of potential therapies against Leishmania and Trypanosoma parasites. (2) develop a concise and modular synthetic strategy, to access the natural products targets from cheap starting materials and allowing scaffold diversification to facilitate SAR studies. This work is important because Visceral Leishmaniasis (VL) affects ~12 million people worldwide and is the second biggest parasitic killer after malaria (20-30000 deaths/year). Chagas disease (CD) affects ~6-7 million people worldwide and is also fatal if untreated (10000 deaths/year). In this project, we aim to show that natural products can serve as an alternative, viable source of candidates for future development as antiparasitic therapies. Throughout medicine, natural products are proven sources of drugs, either in their natural form, as semi-synthetic derivatives, or as analogues which retain the core framework of the natural molecule; it is well-recognized that some two-thirds of small molecule drugs originate from natural bioactive leads. Parasitic diseases are no exception: the frontline treatments for both malaria (artemisinin), and VL (amphotericin B) are natural products, while natural product-inspired therapies are of equal proven utility (such as the quinine analogues chloroquine and mefloquine).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordКоординаторОбединеното кралство