Structure-activity relationships for a class of selective inhibitors of the major cysteine protease from Trypanosoma cruzi


Autoria(s): GUIDO, Rafael Victório Carvalho; TROSSINI, Gustavo H. G.; CASTILHO, Marcelo S.; OLIVA, Glaucius; FERREIRA, Elizabeth I.; ANDRICOPULO, Adriano Defini
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2008

Resumo

Chagas` disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. Cruzain, the major cysteine protease from Trypanosoma cruzi, is an attractive target for antitrypanosomal chemotherapy. In the present work, classical two-dimensional quantitative structure-activity relationships (2D QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 45 thiosemicarbazone and semicarbazone derivatives as inhibitors of T. cruzi cruzain. Significant statistical models (HQSAR, q2=0.75 and r2=0.96; classical QSAR, q2=0.72 and r2=0.83) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 10 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, [image omitted]=0.95; classical QSAR, [image omitted]=0.91), indicating the existence of complementary between the two ligand-based drug design techniques.

FAPESP (The State of Sao Paulo Research Foundation)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESB (The State of Bahia Research Foundation)

Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)

CNPq (The National Council for Scientific and Technological Development), Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Identificador

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, v.23, n.6, p.964-973, 2008

1475-6366

http://producao.usp.br/handle/BDPI/30067

10.1080/14756360701810322

http://dx.doi.org/10.1080/14756360701810322

Idioma(s)

eng

Publicador

INFORMA HEALTHCARE

Relação

Journal of Enzyme Inhibition and Medicinal Chemistry

Direitos

restrictedAccess

Copyright INFORMA HEALTHCARE

Palavras-Chave #Chagas` disease #enzyme inhibitors #drug design #chemotherapy #QSAR #X RECEPTOR ACTIVATORS #PURINE NUCLEOSIDE PHOSPHORYLASE #DRUG DISCOVERY #NEGLECTED DISEASES #HOLOGRAM QSAR #SERIES #LIMITATIONS #STRATEGIES #TARGETS #Biochemistry & Molecular Biology #Chemistry, Medicinal
Tipo

article

original article

publishedVersion