Therapeutic targets for the development of anti-trypanosoma cruzi drugs: A brief review

Chagas disease is a neglected disease caused by Trypanosoma cruzi (T. cruzi) that remains a serious public health problem in Latin America since there are approximately 7 million infected peo‑ ple, making it a matter of worldwide concern. Advances in new therapeutic strategies to combat Cha‑ gas disease have been scarce over the last decades. Efforts have been made to explore T. cruzi en‑ zymes as potential therapeutic targets. Inhibitors that act on enzymes such as triose phosphate isomer‑ ase (TIMTc), glyceraldehyde 3-phosphate dehydrogenase (GAPDHTc), trypanothione reductase (TR), cruzipain, squalene synthase (SQSTc), farnesyl pyrophosphate synthase (FPPSTc) and sterol 14 α-demethylase (CYP51Tc) of T. cruzi have been studied to develop selective inhibitors that interrupt the lifecycle of T. cruzi. These selected drug targets are part of indispensable T. cruzi survival systems such as the glycolysis pathway, cellular detoxification, the host adhesion complex and sterol synthesis pathways, which exhibit relevant features useful in the design of selective inhibitors that may be useful for treating Chagas disease. This review discusses recent progress in the exploration of these enzymes as therapeutic targets and their relevant structural features to develop new drugs against American trypanosomiasis.