Structural Insight into Privileged Heterocycles as Anti-Trypanosoma cruzi and brucei Agents

Trypanosomiasis is caused by parasitic protozoan trypanosomes in vertebrates. T. cruzi and T. brucei are causative agents of Chagas disease (CD) and Human African Trypanosomiasis (HAT), respectively. These life-threatening diseases are a serious threat to public health, with considerable incidence in sub-Saharan African and continental Latin America countries. Although WHO validated mitigated number of HAT cases in Togo (June 2020) and Cote d'Ivoire (December 2020), serious efforts need to be performed for the elimination of the disease. Antigenic variation of trypanosomal parasites provides a major bottleneck for developing effective vaccines. In the absence of human vaccines or chemoprophylaxis, the control of trypanosomatid infections may be envisaged through the eradication of vectors, management of animal reservoirs, and chemotherapy. A small number of chemical agents are currently available for antitrypanosomal treatments, and most of them are associated with toxicity, lack of efficacy, and non-oral route of administration. Given the restricted applicability of current medications, numerous efforts have been made for the synthesis and biological evaluation of heterocyclic scaffolds as antitrypanosomal candidates. In light of the above considerations, we were prompted to describe chemical diversity within privileged 5- membered heterocycles (imidazoles, thiazoles, triazoles and tetrazoles) as antitrypanosomal agents. The main purpose of the study was to throw light on the structure-activity relationship (SAR) of the relevant structures. To capture the recent structural diversity within reported cases, small molecules that belonged to the recent 7-year period (2015-2021) have been discussed. The available medications have also been briefly reviewed.