title: Thiosemicarbazones as Aedes aegypti larvicidal.
abstract: 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.
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil. Electronic address: paraiso@ufpe.br.
authors.forename: João Bosco P
authors.initials: JB
authors.lastname: da Silva
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil. Electronic address: dmafn@ufpe.br.
authors.forename: Daniela Maria do A F
authors.initials: DM
authors.lastname: Navarro
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Aluizio G
authors.initials: AG
authors.lastname: da Silva
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Geanne K N
authors.initials: GK
authors.lastname: Santos
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Kamilla A
authors.initials: KA
authors.lastname: Dutra
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Diogo Rodrigo
authors.initials: DR
authors.lastname: Moreira
authors.affiliation: Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Mozart N
authors.initials: MN
authors.lastname: Ramos
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: José Wanderlan P
authors.initials: JW
authors.lastname: Espíndola
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: Ana Daura T
authors.initials: AD
authors.lastname: de Oliveira
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: Dalci José
authors.initials: DJ
authors.lastname: Brondani
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: Ana Cristina L
authors.initials: AC
authors.lastname: Leite
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: Marcelo Zaldini
authors.initials: MZ
authors.lastname: Hernandes
authors.affiliation: Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil.
authors.forename: Valéria R A
authors.initials: VR
authors.lastname: Pereira
authors.affiliation: Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: da Rocha
authors.affiliation: Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil.
authors.forename: Maria Carolina A B
authors.initials: MC
authors.lastname: de Castro
authors.affiliation: Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil.
authors.forename: Beatriz C
authors.initials: BC
authors.lastname: de Oliveira
authors.affiliation: Department of Entomology, University of Wisconsin-Madison, 1630 Linden Drive, Madison, WI 53706, USA.
authors.forename: Que
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Quantum Theory Project, University of Florida, 2234 New Physics Building, Gainesville, PO Box 118435, Florida, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Merz
mesh_terms: D000330:Aedes / Q000187:drug effects*; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D007814:Larva / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013154:Spleen / Q000166:cytology; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D013882:Thiosemicarbazones; C072087:sterol carrier proteins
keywords: Aedes aegypti; Docking; Larvicide; QSAR; Sterol carrier protein-2; Thiosemicarbazones