| Autor: |
Neto MFA; Laboratório de Quimioinformática e Avaliação Biológica, Departamento de Saúde, Universidade Estadual de Feira de Santana, Feira de Santana 44036-900, Brazil., Campos JM; Departamento de Química Farmacéutica y Orgánica, Universidad de Granada, 18071 Granada, Spain.; Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18071 Granada, Spain., Cerqueira APM; Laboratório de Quimioinformática e Avaliação Biológica, Departamento de Saúde, Universidade Estadual de Feira de Santana, Feira de Santana 44036-900, Brazil., de Lima LR; Laboratório de Modelagem e Química Computacional, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapá 68902-280, Brazil., Da Costa GV; Laboratório de Modelagem e Química Computacional, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapá 68902-280, Brazil., Ramos RDS; Laboratório de Modelagem e Química Computacional, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapá 68902-280, Brazil., Junior JTM; Centro Multidisciplinar, Departamento de Saúde, Universidade Federal do Oeste da Bahia, Barreiras 47100-000, Brazil., Santos CBR; Laboratório de Modelagem e Química Computacional, Departamento de Ciências Biológicas e da Saúde, Universidade Federal do Amapá, Macapá 68902-280, Brazil., Leite FHA; Laboratório de Quimioinformática e Avaliação Biológica, Departamento de Saúde, Universidade Estadual de Feira de Santana, Feira de Santana 44036-900, Brazil. |
| Abstrakt: |
The Aedes aegypti mosquito is the main hematophagous vector responsible for arbovirus transmission in Brazil. The disruption of A. aegypti hematophagy remains one of the most efficient and least toxic methods against these diseases and, therefore, efforts in the research of new chemical entities with repellent activity have advanced due to the elucidation of the functionality of the olfactory receptors and the behavior of mosquitoes. With the growing interest of the pharmaceutical and cosmetic industries in the development of chemical entities with repellent activity, computational studies (e.g., virtual screening and molecular modeling) are a way to prioritize potential modulators with stereoelectronic characteristics (e.g., pharmacophore models) and binding affinity to the AaegOBP1 binding site (e.g., molecular docking) at a lower computational cost. Thus, pharmacophore- and docking-based virtual screening was employed to prioritize compounds from Sigma-Aldrich® (n = 126,851) and biogenic databases (n = 8766). In addition, molecular dynamics (MD) was performed to prioritize the most potential potent compounds compared to DEET according to free binding energy calculations. Two compounds showed adequate stereoelectronic requirements (QFIT > 81.53), AaegOBP1 binding site score (Score > 42.0), volatility and non-toxic properties and better binding free energy value (∆G < −24.13 kcal/mol) compared to DEET ((N,N-diethyl-meta-toluamide)) (∆G = −24.13 kcal/mol). |
