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 (R) and SciFinder (R) databases, in.sdf format. Chemical structures were converted to pdbqt format by the OpenBabel GUI (R) program. Macromolecular target SCP-2 (PDB ID: 1PZ4) was extracted from the RSCB-PDB (R) 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 A. 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.