Ovicidal Activity of 2-Hydroxy-4-Methoxybenzaldehyde, Derivatives and Structural Analogues on Anopheles gambiae Eggs

Abstract

Effective remedies for disrupting An. gambiae metamorphosis at the egg stage are crucial in suppression of the malaria vector populations that result in the reduction of disease burden. 2-Hydroxy-4-methoxybenzaldehyde (the major component of Mondia whytei roots), its derivatives, structural analogues and their blends were evaluated against the eggs of An. gambiae in the search for ovicidal compounds with potential use in mosquito control programs. Mature roots were harvested from Mondia whytei (Hook) Skeels (Asclepiadaceous) plants grown in the Center for African Medicinal and Nutritional Flora and Fauna (CAMNFF) herbal medicinal garden and cleaned with distilled water. 2-Hydroxy-4-methoxybenzaldehyde (1) was isolated by steam distillation of the chopped roots. The selected derivatives and/or analogues were prepared using established chemical procedures and their structures confirmed by NMR spectroscopy and ESI-MS. Ovicidal activity of the pure compounds, derivatives, structural analogues and/or formulated blends was tested at 1, 10, 25 and 50 parts per million (ppm) on An. gambie eggs. Eleven mono-substituted (3–7), di-substituted (8–10), tri-substituted (1-2) aromatic compounds were assayed for ovicidal activity against Anopheles gambiae eggs singly or as blends. Benzaldehyde (4) and 4-methoxybenzaldehyde (9) were further converted into 2-hydroxy-1, 2-diphenylethanone (11), 1, 5-diphenylpenta-1, 4-diene-3-one (12) and 1, 5-bis (4-methoxyphenyl) penta-1, 4-diene-3-one (13) and evaluated for ovicidal activity individually or as blends. Of the 13 compounds evaluated individually, 2-hydroxy-4-methoxybenzaldehyde (1) exhibited the highest ovicidal activity at LC50 0.7075 ppm while anisole had the lowest activity at LC50 40.342 ppm. The derivatives exhibited moderate activity: 2-hydroxy-1, 2-diphenylethanone (LC50 10.599 ppm), 1, 5-diphenylpenta-1, 4-diene-3-one (LC50 9.019 ppm) and 1, 5-bis (4-methoxyphenyl) penta-1, 4-diene-3-one (LC50 15.642 ppm). The blends exhibited intriguingly high ovicidal efficacy with the mixture of benzaldehyde and phenol showing the highest (LC50 0.332 ppm) while phenol and anisole exhibited the lowest activity (LC50 9.9909 ppm). From the activity of the blends, it is evident that anisole is antagonistic to the efficacy of phenol and benzaldehyde. It is also apparent that aldehyde and hydroxyl groups, when directly attached to the phenyl ring, provide the critical structural characteristics that contribute to the ovicidal activity of the aromatic compounds.