Autor(es): da Silva João Bosco P,Navarro Daniela Maria do A F,da Silva Aluizio G,Santos Geanne K N,Dutra Kamilla A,Moreira Diogo Rodrigo,Ramos Mozart N,Espíndola José Wanderlan P,de Oliveira Ana Daura T,Brondani Dalci José,Leite Ana Cristina L,Hernandes Marcelo Zaldini,Pereira Valéria R A,da Rocha Lucas F,de Castro Maria Carolina A B,de Oliveira Beatriz C,Lan Que,Merz Kenneth M

Resumo: A set of aryl- and phenoxymethyl-(thio)semicarbazones were synthetized, characterized and biologically evaluated against the larvae of Aedes aegypti (A. aegypti), the vector responsible for diseases like Dengue and Yellow Fever. (Q)SAR studies were useful for predicting the activities of the compounds not included to create the QSAR model as well as to predict the features of a new compound with improved activity. Docking studies corroborated experimental evidence of AeSCP-2 as a potential target able to explain the larvicidal properties of its compounds. The trend observed between the in silico Docking scores and the in vitro pLC50 (equals -log LC50, at molar concentration) data indicated that the highest larvicidal compounds, or the compounds with the highest values for pLC50, are usually those with the higher docking scores (i.e., greater in silico affinity for the AeSCP-2 target). Determination of cytotoxicity for these compounds in mammal cells demonstrated that the top larvicide compounds are non-toxic.

Palavras-Chave: Aedes aegypti; Docking; Larvicide; QSAR; Sterol carrier protein-2; Thiosemicarbazones

Imprenta: European Journal of Medicinal Chemistry, v. 100, p. 162-175, 2015

Identificador do Objeto Digital: 10.1016/j.ejmech.2015.04.061

Descritores: Aedes aegypti - Cell ; Aedes aegypti - Larvicide ; Aedes aegypti - Dengue

Data de Publicação: 2015