Thiosemicarbazones as Aedes aegypti larvicidal

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

doi:10.1016/j.ejmech.2015.04.061

Thiosemicarbazones as Aedes aegypti larvicidal

Eur J Med Chem. 2015 Jul 15:100:162-75. doi: 10.1016/j.ejmech.2015.04.061. Epub 2015 May 28.

Authors

João Bosco P da Silva¹, Daniela Maria do A F Navarro², Aluizio G da Silva³, Geanne K N Santos³, Kamilla A Dutra³, Diogo Rodrigo Moreira³, Mozart N Ramos³, José Wanderlan P Espíndola⁴, Ana Daura T de Oliveira⁴, Dalci José Brondani⁴, Ana Cristina L Leite⁴, Marcelo Zaldini Hernandes⁴, Valéria R A Pereira⁵, Lucas F da Rocha⁵, Maria Carolina A B de Castro⁵, Beatriz C de Oliveira⁵, Que Lan⁶, Kenneth M Merz Jr⁷

Affiliations

¹ 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.
² 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.
³ Departamento de Química Fundamental, Centro de Ciências Exatas e da Natureza, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
⁴ Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
⁵ Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil.
⁶ Department of Entomology, University of Wisconsin-Madison, 1630 Linden Drive, Madison, WI 53706, USA.
⁷ Quantum Theory Project, University of Florida, 2234 New Physics Building, Gainesville, PO Box 118435, Florida, USA.

PMID: 26087027
DOI: 10.1016/j.ejmech.2015.04.061

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.

Keywords: Aedes aegypti; Docking; Larvicide; QSAR; Sterol carrier protein-2; Thiosemicarbazones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aedes / drug effects*
Animals
Carrier Proteins / antagonists & inhibitors*
Dose-Response Relationship, Drug
Larva / drug effects
Mice
Mice, Inbred BALB C
Molecular Structure
Quantitative Structure-Activity Relationship
Spleen / cytology
Thiosemicarbazones / chemical synthesis
Thiosemicarbazones / chemistry
Thiosemicarbazones / pharmacology*

Substances

Carrier Proteins
Thiosemicarbazones
sterol carrier proteins