Chagas disease is caused by the protozoan Trypanosoma cruzi and is endemic in regions of Latin America. The drugs used most extensively for the treatment of Chagas disease are benznidazole and nifurtimox. Neither of these drugs has been shown to eradicate infection during the chronic phase when most patients are diagnosed. While the search for the novel drug targets and new lead structures for the treatment of Chagas disease is of critical importance, a complimentary strategy is to utilise and further develop lead structures from nature with proven biological activity. Quinine, an alkaloid derived from the bark of the cinchona tree, is highly effective against parasitic infections despite almost 400 years of use. Quinine is a potent molecule completely inhibiting T. cruzi epimastigote replication in vitro. Interaction with DNA would seem to be a reasonable mechanistic hypothesis. Using the Heck reaction, we have pursued modification of the vinyl group in quinine. We have also targeted the 2-position using Suzuki chemistry to develop novel quinine analogues. Following molecular-docking studies on Trypanosoma cruzi trypanothione reductase (TcTR) (PDB Id: 1GXF) and energy minimisation of the ligands, our quinine analogues have displayed excellent binding affinity. These results will be used to generate promising drug candidates for future clinical use.