Collaborative Synthesis for Neglected Diseases through the Open Synthesis Network: Structure–Activity Relationships of Arylaminopyrazoles as Chagas Disease Treatments

Neglected tropical diseases (NTDs) make up a diverse
group of debilitating
illnesses disproportionately affecting impoverished communities in
tropical and subtropical regions. Despite their significant global
health burden, they are often overshadowed by more prominent diseases,
resulting in a critical lack of investment in the research and development
of new treatments. A renewed focus on NTDs is, therefore, urgently
needed, particularly in terms of novel therapeutic strategies. The
Open
Synthesis Network, launched by DNDi and partner institutions in 2016,
is an innovation powerhouse that taps into the potential of students
to help drive the discovery of new drugs for patients living with
NTDs. We present the results of student-led work into the development
of a series of aminopyrazoles for Chagas disease, a multisystemic
disease caused by the Trypanosoma cruzi parasite. Seventy-four compounds were synthesized by undergraduate
and postgraduate students from six universities from Brazil, Ghana,
Germany, USA, and UK, illustrating that open innovation and collaboration
for education can drive drug discovery forward. Early evaluation of
the structure–activity relationships identified a range of
potent hit compounds with selectivity for T. cruzi and no observable cytotoxicity.