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

Author(s)

Pernichelle, Filipe Gomes ; Alves, Erick Tavares Marcelino ; Serafim, Ricardo Augusto Massarico ; Ferreira, Elizabeth Igne

• Document type: Journal article
• Source: CHEMISTRYSELECT; v. 8, n. 33, p. 25-pg., 2023-09-05.

Abstract

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. Piperazine has been used in many therapeutical classes, including tropical neglected diseases, as Chagas disease. This review summarized and exemplified the role of this linker interacting with some of the targets that have been studied for the development of trypanomicide drugs, as nitroreductase, cruzain, trypanothione reductase, Cyp51 and Fe-superoxide dismutase. The examples could inspire authors who works on the design of trypanomicide drugs.image (AU)

• FAPESP's process: 20/13347-2 - Potentially active anti-chagas disease: design and synthesis of molecular hybrids of enzymes as fe-superoxide dismutase and CYP51 with nitric oxide releasing groups
• Grantee: Filipe Gomes Pernichelle
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 21/04778-2 - Potentially active anti-chagas disease: design and synthesis of molecular hybrid of enzymes superoxide dismutase and CYP51 with nitric oxide releasing group
• Grantee: Erick Tavares Marcelino Alves
• Support Opportunities: Scholarships in Brazil - Scientific Initiation