Multiparameter Optimization of Trypanocidal Cruzain Inhibitors With In Vivo Activity and Favorable Pharmacokinetics

Autor: Ivani Pauli, Celso de O. Rezende Jr., Brian W. Slafer, Marco A. Dessoy, Mariana L. de Souza, Leonardo L. G. Ferreira, Abraham L. M. Adjanohun, Rafaela S. Ferreira, Luma G. Magalhães, Renata Krogh, Simone Michelan-Duarte, Ricardo Vaz Del Pintor, Fernando B. R. da Silva, Fabio C. Cruz, Luiz C. Dias, Adriano D. Andricopulo

Publikováno v: Frontiers in Pharmacology, Vol 12 (2022)

Cruzain, the main cysteine protease of Trypanosoma cruzi, plays key roles in all stages of the parasite’s life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition

Externí odkaz: https://doaj.org/article/8b05c18bef4c4cee9ab7ee11d594e168

Chemoinformatics Studies on a Series of Imidazoles as Cruzain Inhibitors

Autor: Alex R. Medeiros, Leonardo L. G. Ferreira, Mariana L. de Souza, Celso de Oliveira Rezende Junior, Rocío Marisol Espinoza-Chávez, Luiz Carlos Dias, Adriano D. Andricopulo

Publikováno v: Biomolecules, Vol 11, Iss 4, p 579 (2021)

Natural products based on imidazole scaffolds have inspired the discovery of a wide variety of bioactive compounds. Herein, a series of imidazoles that act as competitive and potent cruzain inhibitors was investigated using a combination of ligand- a

Externí odkaz: https://doaj.org/article/062067ec742e4137ad2cf1b9f35187a7

Chemoinformatics Studies on a Series of Imidazoles as Cruzain Inhibitors

Autor: Adriano D. Andricopulo, Leonardo L. G. Ferreira, Rocío Marisol Espinoza-Chávez, Alex R. Medeiros, Luiz C. Dias, Mariana L. de Souza, Celso O. R. Junior

Publikováno v: Biomolecules
Volume 11
Issue 4
Biomolecules, Vol 11, Iss 579, p 579 (2021)
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP

Natural products based on imidazole scaffolds have inspired the discovery of a wide variety of bioactive compounds. Herein, a series of imidazoles that act as competitive and potent cruzain inhibitors was investigated using a combination of ligand- a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52709e7193088b5c7faa364ea8c4f676

Carbamoyl Imidazoles As Potent, Reversible and Competitive Cruzain Inhibitors with in vitro and in vivo Trypanocidal Activity: A Structure-Based Drug Design Approach

Autor: Adriano D. Andricopulo, Celso O. R. Junior, Brian W. Slafer, Luma G. Magalhães, Rocio Marisol Espinoza Chávez, Glaucius Oliva, Fabio C. Cruz, Luiz C. Dias, Leonardo L. G. Ferreira, Renata Krogh, Rafaela Salgado Ferreira, Mariana L. de Souza

Publikováno v: SSRN Electronic Journal.

A virtual screening conducted with nearly 4,000,000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzi cruzain enzyme, a validated drug target for Chagas disease. S

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::827a1f7d61ccc3cee45fd5c4d0f81ed2
https://doi.org/10.2139/ssrn.3387684

Synthesis, biological evaluation, and structure-activity relationships of potent noncovalent and nonpeptidic cruzain inhibitors as anti-Trypanosoma cruzi agents

Autor: Glaucius Oliva, Ivani Pauli, Luiz C. Dias, Mariana L. de Souza, Rafaela Salgado Ferreira, Renata Krogh, Ana Isabela Lopes Sales, Marco A. Dessoy, Adriano D. Andricopulo

Publikováno v: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP

The development of cruzain inhibitors has been driven by the urgent need to develop novel and more effective drugs for the treatment of Chagas' disease. Herein, we report the lead optimization of a class of noncovalent cruzain inhibitors, starting fr

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a5924cf5c49dfdae3312d4f0d18e8eb
https://pubmed.ncbi.nlm.nih.gov/24533839