Potentially active anti-chagas disease: design and synthesis of molecular hybrids of enzymes as fe-superoxide dismutase and CYP51 with nitric oxide releasing groups

• Grant number: 20/13347-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2021
• End date: August 31, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Elizabeth Igne Ferreira
• Grantee: Filipe Gomes Pernichelle
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/00283-1 - Design and synthesis of 7-azaindole derivatives with potential trypanocidal activity, BE.EP.MS

Abstract

Chagas disease is considered extremely neglected by the World Health Organization, as it raises low interest to the introduction of new drugs in therapeutics. There are two drugs used in the treatment: nifurtimox and benznidazole. In Brazil, only benznidazole has been used. Due to the need of new and better drugs against this parasitosis, mainly in its chronic phase, this project aim to synthesize molecular hybrids, which can act through three different mechanisms of action: NO release by furoxane group, changing cruzain activity; CYP51 inhibition, due to the disubstituted aromatic group, able to interact with the active site of the enzyme, and through the inhibition of Fe-SOD, by the presence of piperazine group, which interacts with this enzyme. This design can be considered as an example of polypharmacology, extensively used nowadays, as it implies more efficacy of the compounds designed to a determined disease. The compounds will be synthesized in 5 steps and, once obtained, they will be submitted to trypanomicide in vitro assays. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PERNICHELLE, FILIPE GOMES; ALVES, ERICK TAVARES MARCELINO; SERAFIM, RICARDO AUGUSTO MASSARICO; FERREIRA, ELIZABETH IGNE. The Importance of the Piperazine Ring for the Development of Trypanomicide Compounds. CHEMISTRYSELECT, v. 8, n. 33, p. 25-pg., 2023-09-05. (20/13347-2, 21/04778-2)

ALVES, ERICK TAVARES MARCELINO; PERNICHELLE, FILIPE GOMES; NASCIMENTO, LUCAS ADRIANO; FERREIRA, GLAUCIO MONTEIRO; FERREIRA, ELIZABETH IGNE. Covalent Inhibitors for Neglected Diseases: An Exploration of Novel Therapeutic Options. PHARMACEUTICALS, v. 16, n. 7, p. 40-pg., 2023-07-01. (20/13347-2, 21/04778-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PERNICHELLE, Filipe Gomes. Potential anti-chagasic agents: design and synthesis of molecular hybrids and azaindoles. 2023. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.