Identification of molecular scaffolds from Caatinga Brazilian biome with potential against Aedes aegypti by molecular docking and molecular dynamics simulations

Abstract

In this paper, we performed a virtual screening by docking and molecular dynamics approaches to identify molecular scaffolds as potential inhibitors of the Sterol Carrier Protein-2 (PDB ID: 1PZ4) from Aedes aegypti, using a homemade data bank of 248 secondary metabolites, found on Caatinga Brazilian biome. The insect is a known vector of important diseases around the world, as Zika, Chikungunya and Dengue fever. The compounds were selected after a search on SciFinderⓇ online platform, crossing the name of 40 Caatinga biome plants with words indicating the identification and/or isolation of molecules. Initial re-docking and docking procedures showed that the co-crystalized ligand (“palmitic acid”) presented a binding energy (-6.9 kcal/mol) higher than seventy-six of the total number of compounds evaluated (two hundred forty-eight). Five compounds were considered for sequential Molecular Dynamics (MD) calculations, by energetic and structural analysis. The MD plots and average binding energies obtained by MM/PBSA method confirm that the biflavonoid loniflavone, founded in the leaves of a Brazilian plant called “catingueira” (Cenostigma pyramidale (Tul.) E. Gagnon & G. P. Lewis, previously Caesalpinia priamidalis) was the most promissory in the interaction with 1PZ4. Two additional compounds from lignan and sesquiterpene molecular scaffolds were also identified as potential against A. aegypti. These results can be used as guidelines for testing compounds with larvicidal application.