Application of Structure-Based Drug Design in parasite cysteine protease inhibitor search (cruzain (T. cruzi and CPB (Leishmanioses))

• Grant number: 13/15650-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2014
• End date: June 30, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Gustavo Henrique Goulart Trossini
• Grantee: Drielli Gomes Vital Fujii
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 17/01181-0 - Virtual Screening (VS) and High-Throughput Screening (HTS) integration in discovery of new drugs against neglected tropical diseases (NTDs), BE.EP.DR

Abstract

Caused by infectious and parasitic agents, neglected diseases are responsible for bringing millions of people to death every year and primarily affect poor countries and developing countries, not arousing the interest of pharmaceutical industries to develop new therapies. Among these, Chagas disease and Leishmaniasis, caused by parasitic flagellate parasites belonging to the family Trypanosomatidae, T. cruzi and Leshmania sp. respectively, are presented as a serious public health problem worldwide. Even endemic in several countries and causing millions of deaths every year, there are still no effective and safe drugs for its treatment. This panorama makes eminent the need for research and development of new drugs for these parasites. The search for chemotherapeutic agents involves the selection of metabolic pathways essential for parasite survival, highlighting the cysteine proteases present in these trypanosomes. The cruzain in T. cruzi and CPB in Leishmaniasis thus appear as biochemical targets promising. The availability of crystallographic structures of cruzain and genomic sequencing of CPB, allows us to use strategies of drug design based on receptor (SBDD) to identify drug candidates for these diseases. Among the modern techniques used SBDD, the virtual screening helps identify and select potent and selective enzyme inhibitors. Thus, it is proposed in this project, from design through SBDD inhibitors cruzain (virtual screening) and CPB (Comparative Modeling / Virtual Screening) and biological assays (enzymatic and parasitic) in identifying candidates trypanocides and antileishmanial agents.

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)

GOMES, RENAN AUGUSTO; FORNARI, EVELIN; SILVA ROCHA, ANA CAROLINA; TRIPODI, GUSTAVO LUIS; DA SILVA EMERY, FLAVIO; GOULART TROSSINI, GUSTAVO HENRIQUE. Parasitic sirtuin 2 as an opportunity in drug discovery. Future Medicinal Chemistry, v. 13, n. 16, p. 1397-1409, AUG 2021. (17/06568-0, 13/15650-0, 17/25543-8)

MOURA GATTI, FERNANDO DE; GOMES, RENAN AUGUSTO; DA FONSECA, AMANDA LUISA; CARDOSO LIMA, ELYS JULIANE; VITAL-FUJII, DRIELLI GOMES; TARANTO, ALEX GUTERRES; PILLA VAROTTI, FERNANDO DE; GOULART TROSSINI, GUSTAVO HENRIQUE. Antiplasmodial activity of sulfonylhydrazones: in vitro and in silico approaches. Future Medicinal Chemistry, v. 13, n. 3, p. 233-250, FEB 2021. (13/15650-0, 17/25543-8)

Academic Publications

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

FUJII, Drielli Gomes Vital. Structure-based virtual screening in the search of parasitic cysteine-proteases inhibitors. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.