Protozoa are a group of single-celled eukaryotes, either free-living or parasitic, that can cause disease in both humans and animals such as trypanosomiasis and histomoniasis. Current antiprotozoal treatments are often ineffective, require a suboptimal compound administration route, face increasing resistance and are endowed with concerns about toxicity (direct and indirect). Therefore, novel treatment options are needed to treat a large variety of protozoan-caused infections.
For example, the incidence and severity of histomoniasis outbreaks in turkeys is increasing in the EU and US, with high morbidity and mortality sometimes approaching 100 % of a flock. This disease represents a severe and ongoing animal health and welfare problem to the poultry population and therefore to a significant sector of the poultry industry. However, there are currently no authorised medicines for treatment or prevention in the EU.
Protozoa are unable to synthesize certain molecules required for synthesis of their DNA such as purines. They instead rely on the uptake and interconversion of these molecules from the host, making purine nucleoside analogues as a potential source of antiprotozoal agents. The Laboratory for Medicinal Chemistry at Ghent University has prepared a purine nucleoside platform based on known and novel sugar- and purine ring scaffolds. In collaboration with the Lab of Molecular Parasitology and Hygiene of the Univerrsity of Antwerp, it was demonstrated that these purine nucleoside analogues can act as potent antiprotozoal agents. Furthermore, nucleoside chemistry has already been extensively validated for its safety in antiviral indications in human medicine.
As an example, we found 3’-deoxytubercidin analogues to be highly potent against Trypansoma brucei subspecies. One analogue served as proof-of-concept in relevant mouse model of T. brucei infection. This derivative, 3’-deoxytubercidin, displays curative activity in both acute and CNS-stage infection in mice, highlighting that it is able to cross the blood-brain-barrier, likely a class effect. Nucleoside analogue compound 9 shows excellent efficacy in murine human African trypanosomiasis (HAT) models (acute and central nervous system). Additionally, in vivo proof-of-concept for several other protozoal infections (T. cruzi, T. vaginalis) has been obtained.
Partners we search for
We seek development and marketing partners interested in developing nucleoside analogues as anti-parasitic against protozoal infections. We have several additional indications under investigation, such as leishmaniasis, Chagas disease, Nagana disease, blackhead disease, cryptosporidosis and toxoplasmosis. We can offer a focused purine nucleoside library, containing >600 diverse nucleoside analogues in 96-well plate format for screening purposes.
About the researchers/research group
The Laboratory of Microbiology, Parasitology and Hygiene (LMPH) is an interdepartmental research group at the Faculty of Pharmaceutical, Biomedical and Veterinary Sciences at the University of Antwerp. Our research is focused on pathogen host interactions, with Leishmania, Bacterial biofilms and Respiratory Syncytial Virus being the main research themes. In addition, attention is given to modulation of macrophages upon interaction and/or infection with pathogens. Besides basic research, we have extensive, documented experience in integrated antimicrobial screening, both for industry and academic groups, of chemical and natural products. This screening is performed with in-house developed, validated in vitro and vivo laboratory models of bacteria, yeasts, fungi and parasites.
The Laboratory of Medicinal Chemistry (UGhent) utilizes synthetic organic chemistry in conjunction with developments in biochemistry, computational chemistry, molecular biology, and pharmacology to advance drug discovery. In our laboratory problems at the chemistry-life sciences interface are addressed. A large part of our work concentrates on the development of small molecule modulators of new targets. These modulators can be both enabling chemical tools to interrogate biology or therapeutically useful compounds. From a chemical point of view, much of our work is centered on the chemical synthesis of novel nucleoside and sphingolipid analogues. Our research interest also includes carbohydrate, phosphonate and bioconjugate chemistry. Several of the running projects deal with the design of new lead structures for the treatment of infectious diseases with unmet medical needs (e.g. malaria and TB).
For this technology offer UGhent is in the lead, interested parties can contact:
Dr. ir. Sven Arnouts, RTTP
Business Development Manager PROVAXS – Ghent University
Salisburylaan 133, 9820 Merelbeke, Belgium
Tel. : +32 9 264 73 33
Mob. : +32 495 707 334
Email : Sven.Arnouts@UGent.be