Virtual Screening of Fargesin Analogs as Candidates as Inhibitors of Aedes aegypti Sterol Carrier Protein

Background: Fargesin is a natural product that was identified by our group in previous work as a potent ligand of the sterol-binding protein-2 (SCP-2) of Aedes aegypti, the mosquito that which causes the propagation of diseases such as zika, dengue, Chikungunya, and yellow fever. Objectives: propose structural analogs synthetically accessible to be evaluated by molecular docking, preserving the fargesin privileged group’s benzodioxol and methoxybenzene, with different spacer groups. Materials and Methods: Structures were obtained in PubChem® and SciFinder® databases, in .sdf format. Chemical structures were converted to pdbqt format by the OpenBabel GUI® program. Macromolecular target SCP-2 (PDB ID: 1PZ4) was extracted from the RSCB-PDB® platform, and molecular docking was performed using the Autodock vina program. The target binding site was defined based on the crystallographic ligand (palmitic acid), with grid box dimensions 16x12x18 Å. Results: The database built had 1231 molecules, with molecules that had binding energy lower than -6.9 Kcal/mol considered valid results. Thus, of the 447 molecules that were most favorable, the best results were for the compounds: 188 (-12.6 Kcal/mol), 350 (-12.6 Kcal/mol), 351 (-12.3 Kcal/mol), 773 (-12.3 Kcal/mol) and 831 (-12.1 Kcal/mol). Conclusion: The results of this paper showed that isoflavonoids synthetically acessible are promising candidates for larvicidal agents, which corroborates with other published data from our research group and encourages experimental investigations.