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

Author:

Gomes Pernichelle Filipe1,Tavares Marcelino Alves Erick1,Massarico Serafim Ricardo Augusto2,Igne Ferreira Elizabeth1ORCID

Affiliation:

1. School of Pharmaceutical Sciences Department of Pharmacy University of Sao Paulo Brazil Av. prof. Lineu Prestes, 580 Bl13/15 São Paulo SP CEP 05508–000

2. Department of Pharmaceutical/Medicinal Chemistry Eberhard-Karls-University Tuebingen Auf der Morgenstelle 8 72076 TübingenTuebingen Germany

Abstract

AbstractChagas 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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Wiley

Subject

General Chemistry

Reference53 articles.

1. WHO World Health Organizationhttps://www.who.int/chagas/en/ 2022(accessed 12 September 2022).

2. DNDi Drugs for Neglected Diseases Initiative2022https://dndial.org/doencas/doenca-de-chagas/(accessed 12 September 2022).

3. PAHO Pan American Health Organizationhttps://www.paho.org/en 2022(accessed 12 September 2022).

4. Use of clomipramine as chemotherapy of the chronic phase of Chagas disease

5. Anti-Trypanosoma cruzi and anti-leishmanial activity by quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives

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