Title:Structural Insight into Privileged Heterocycles as Anti-Trypanosoma cruzi and brucei Agents
Volume: 23
Issue: 9
Author(s): Jafar Abbasi Shiran, Mina Ghanbari, Elaheh Mohammadnejadi and Nima Razzaghi-Asl*
Affiliation:
- Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
Keywords:
Chagas disease, Human African trypanosomiasis, Heterocycles, Structure-activity relationship, Trypanosomiasis, trypanosomal parasites, Brucei agents.
Abstract: 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.
