Synergistic enhancement of natural mosquito repellents through matrix interactions: Insights from GC-MS and bioassays

Abstract

While plant-based mosquito repellents are considered safer alternatives to synthetic chemicals, their short-lived efficacy often diminishes their effectiveness. This study investigates a synergistic approach using a matrix of plant-derived samples to address this limitation and enhance their repellency. In olfactory studies, powdered samples and extracts—both individual and blended—were tested against Anopheles gambiae s.l. and Anopheles funestus in laboratory and semi-field environments. Euclidean distances, Hierarchical clustering, and heatmap analyses assessed compound relationships to repellent compounds that were literature-cited. Molecular fingerprints from SMILES identifiers and Tanimoto coefficients quantified structural similarity. Sample matrices significantly enhanced repellency, demonstrating superior performance in olfactory assays (e.g., Striga hermonthica vs. Lantana camara/S. hermonthica blend: W = 787, p = 0.0013) and extending protection times in human trials (179 vs. 67 minutes, t = 21.872, p < 0.001). GC-MS analysis revealed major compounds for S. hermonthica (Methyl-6-O-[1-methylpropyl]-α-galactopyranoside, 51.047 %), Hyptis spicigera (Cyclopropanecarboxylic acid derivative, 87.137 %), and L. camara (1-Heptatriacotanol, 10.099 %). Phytol and a Phthalic acid derivative were identified, with monoterpenes (−)-Spathulenol and Cis-Z-α-Bisabolene epoxide possibly contributing to synergy. Heatmap and Tanimoto coefficient analyses revealed moderate structural similarities among compounds in active and inactive portions of sample matrices. Key compounds like Phytol and Phthalic acid derivatives, alongside potential synergists such as spathulenol and bisabolene, are hypothesized to contribute to the observed repellency. Long-chain primary alcohol 1-heptatriacotanol holds promise for optimizing plant-based repellents with extended and robust action.