Applications of molecular modeling in the design of new insect repellents targeting the odorant binding protein of Anopheles gambiae

Abstract

Mosquitos são responsáveis pela transmissão de várias doenças causadas por vírus, parasitas e helmintos. Considerando o custo e a complexidade do tratamento dessas doenças, o uso de repelentes para proteção contra mosquitos vetores se torna uma alternativa interessante. Nesse contexto, no presente trabalho foram feitos estudos por ancoramento e dinâmica molecular (DM) de potenciais ligantes da proteína odorante do mosquito Anopheles gambiae (AgOBP 1 ), o principal vetor da malária. Os modos de ligação na AgOBP 1 de moléculas com conhecida atividade atrativa e dos principais componentes do óleo do cravo da índia (Syzygium aromaticum), com potencial atividade repelente, foram comparados com o conhecido repelente N,N-dietil-3-metilbenzamida (DEET). Os resultados sugerem que o acetato de eugenila é um repelente melhor do que o DEET e também revelam as principais características do sítio de ligação da AgOBP 1 importantes para o planejamento de novos e mais eficientes repelentes.Mosquitoes are responsible for conveying various diseases caused by viruses, parasites and helminthes. Considering the cost and complexity of the treatment of these diseases, the use of repellents for protection from the mosquito vectors becomes an interesting alternative. In the present work, docking and molecular dynamics (MD) studies were performed on potential ligands to the odorant binding protein of the mosquito Anopheles gambiae (AgOBP 1 ), the main vector of malaria. The binding modes on AgOBP 1 of molecules with known attractive activities and the main components of the oil of indian clove (Syzygium aromaticum) with potential repellent activities were compared to the known repellent N, . Results suggest the eugenyl acetate as a better repellent than DEET and also reveal the main features of the binding site of AgOBP 1 important to the design of new and more efficient repellents.

Quantification and Characterization of the Main Components of the Ethanolic Extract of Indian Cloves,Syzygium aromaticum[I] Merr. et Perry

“…Estes compostos já tinham sido observados em outros trabalhos, 1,3,6,16,34,42,43 mas por apresentarem-se como componentes minoritários do produto da extração (valor máximo observado foi de 3,2 %) e segundo Affonso et al (2013) 36 por não demonstrarem interações com a proteína AgamOBP1, sua caracterização e quantificação não foi priorizada. O pico correspondente ao t R 9,7 (min.)…”

Quantification through TLC‐densitometric analysis, repellency and anticholinesterase activity of the homemade extract of Indian cloves

“…This is more related to the gender than to DEET, as women present lower levels of lactic acid in the blood even after intense physical activity. The lactic acid is one of the constituents of the human sweat and an important attractant to mosquitoes (Affonso, Guimarães, Oliveira, Slana, & França, ). Our results, reported in Figure , therefore, corroborate literature reports.…”

Ligand binding and homology modelling of insect odorant‐binding proteins

“…Hydrogen bonds are formed via water molecules with Trp114, Cys95 and Gly92 (Tsitsanou et al , ). Although DEET appears to have a specific interaction with the OBP, it was recently reported that eugenyl acetate could be a better repellent than DEET as a result of a better affinity with the binding site of AgamOBP1, as shown by molecular modelling studies (Affonso et al , ). However, binding assays and robust behavioural bioassays are necessary to corroborate those findings.…”