The Importance of the Piperazine Ring for the Development of Trypanomicide Compounds

Chagas disease (CD) is one of extremely Neglected Tropical Diseases (NTD) that have been challenging the health of billions of people in the world. Despite being a threat worldwide many of these diseases have a scarce chemotherapeutic armamentarium and the drugs currently used are not effective because of several reason, such as drug resistance, serious side-effects, among others. Only two drugs are currently available for CD therapeutics, and they are not active in the chronic phase of the diseases. Considering the huge necessity of drugs for this parasitosis, the search for either new or better drugs than those used, many research groups have been involved in this investigation. New scaffolds can be used with this purpose and piperazine is one of them. Since it has many chemical, pharmacological and pharmacokinetics advantages, including multitarget activity, this group has been often used in CD. In this review, which the role of piperazine group in the structure-activity of some important targets for T. cruzi, as cruzain, trypanothione reductase, Fe-superoxide dismutase, and nitroreductase as well, is comprehended, several examples have been given to inspire researchers to optimize either hit or lead compounds against T. cruzi.