Integrated Experimental, Chemometric, and In Silico Analyses of Larvicidal Supercritical Extracts From Myrtaceae Species Against Aedes aegypti.

Supercritical extracts from five Myrtaceae species were evaluated for larvicidal activity against Aedes aegypti (A. aegypti) and investigated through chemical profiling, concentration-response modeling, chemometric analysis, and molecular modeling. Leaf extracts of Corymbia citriodora, Eugenia uniflora (E. uniflora), Plinia cauliflora (P. cauliflora), Psidium cattleianum (P. cattleianum), and Psidium guajava were characterized by GC-MS and tested at 60-300 µg mL- 1 for 72 h. We also performed molecular docking analyses of the identified compounds against two A. aegypti targets, AeSCP-2 (PDB: 1PZ4) and AeHKT (PDB: 6MFB), and Drosophila melanogaster acetylcholinesterase (DmAChE; PDB: 6XYU), a homologous model of insect AChE. All extracts caused mortality, although responses differed among species. P. cattleianum and E. uniflora were highly active across the tested range, whereas P. cauliflora showed weaker, heterogeneous, and non-monotonic responses. PCA revealed marked compositional differences among species but no significant mortality gradient along the first two components. A grouped cross-validated regression tree showed modest predictive performance, indicating associations between covarying chemical profiles and mortality rather than independent compound effects. Docking against AeSCP-2, AeHKT, and DmAChE, followed by molecular dynamics of the AeSCP-2-β-sitosterol complex, identified structurally plausible ligand-target associations. Overall, the study demonstrates species-dependent larvicidal activity and provides experimentally testable hypotheses for prioritizing extracts, compounds, and molecular targets in future investigations.