School of Infection & Immunity

Research involving iii's Professor Harry de Koning that describes a systematic exportation of the structure of lead compounds against African trypanosomiasis has been published in ACS Infectious Diseases.

Human African trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei parasites. These protists are unable to produce the purine ring, making them vulnerable to the effects of purine nucleoside analogues.

Starting from 3'-deoxytubercidin (5), a lead compound with activity against central-nervous-stage human African trypanosomiasis, researchers investigated the structure–activity relationships of the purine and ribofuranose rings.

The lead compound 3'-Deoxytubercidin displayed pronounced activity in a mouse model of the disease, even at low dosage and when administered orally, and when the disease had progressed to the cerebral stage, which is both fatal and hard to treat.

A previous study, published in Nature Communications, detailed how treatment with the nucleoside drug appeared to be both safe and effective.

This most recent paper, published on 22 June, explored systematically whether modifications of the lead molecule could further improve the activity.

The collaboration behind the research is led by Professor Serge van Calenbergh and his postdoc Dr Fabian Hulpia, of Ghent University in Belgium, and includes the group of Professor Guy Caljon at the University of Antwerp and iii researchers.

Structure–Activity Relationship Exploration of 3'-Deoxy-7-deazapurine Nucleoside Analogues as Anti-Trypanosoma brucei Agents

• Fabian Hulpia, Gustavo D. Campagnaro, Khalid J. Alzahrani, Ibrahim A. Alfayez, Marzuq A. Ungogo, Dorien Mabille, Louis Maes, Harry P. de Koning, Guy Caljon, and Serge Van Calenbergh.
• ACS Infectious Diseases DOI: 10.1021/acsinfecdis.0c00105

First published: 29 July 2020