News

Cover Story:
In the New Medicines for Trypanosomatidic Infections (NMTRypI) project funded by the EU, we have discovered novel anti-leishmania and anti-trypanosoma hits that inhibit pteridine reductase 1 (PTR1). Here, we synthesized compounds with a flavanone scaffold and characterized their antiparasitic activity and ADME-tox properties. Crystal structure determination and computational docking explain differences in their inhibition of PTR1. Two crystal structures of one compound with different PTR1 enzymes provide a basis for further scaffold optimization to develop inhibitors targeting PTR1 enzymes from different parasites. Molecules 2017, 22(3), 426; DOI: 10.3390/molecules22030426

Results in brief from Cordis citations:
A special citation of the EU Commission for the results achieved within the project New Medicines for Trypanosomatidic infections, grant number: 603240.

Invitation by the EU Commission:
The EU Commission invited the Coordinators of the FP7 projects to present the project results at the Satellite Symposium on Neglected Infectious Diseases during the ECTMIH 2017 (European Congress on Tropical Medicine and International Health).

Introduction

According to the WHO (Second WHO report on Neglected Tropical Diseases 2013), one billion people are at risk of or are affected by Neglected Tropical Diseases (NTDs), which often affect communities living in remote rural areas or urban slums with poor living and hygiene conditions.

The spread of NTDs like sleeping sickness, leishmaniasis and Chagas disease caused by parasitic microorganisms belonging to the Trypanosomatidae family is a very important issue in some areas of the World, including Africa, South America and India, where these parasites are endemic.

Research on Trypanosomatidic diseases is limited and fragmented and national initiatives are generally weak or lacking critical mass. Problems associated with existing drugs include inefficient delivery, insufficient efficacy, excessive toxicity and increasing resistance. New drugs are urgently needed now and in the near future.

The New Medicines for Trypanosomatidic Infections - NMTrypI project aimed at obtaining new candidate drugs against Trypanosomatidic infections with appropriate efficiency from the lead phase to the final preclinical phase that are more accessible to patients.

The NMTrypI Consortium used a highly interdisciplinary approach to optimize pteridine, thiadiazole/benzothiazole and miltefosine derivatives, as well as natural products, against Trypanosomatids. It was composed of 12 partners: Small and Medium-sized Enterprises (SMEs) (3) and academics (9) in Europe and disease-endemic countries (Italy, Greece, Portugal, Sudan and Brazil; a previous 13th partner, IE, left in June 2016). The research team was coordinated by Maria Paola Costi, professor of Medicinal Chemistry at the University of Modena and Reggio Emilia (UNIMORE).

NMTrypI was an EU-funded three-year research project with a total budget of €7,6 million.

The project was launched on February 1st, 2014 and lasted until January 31st, 2017.