Semi-synthetic cinnamodial analogues: Structural insights into the insecticidal and antifeedant activities of drimane sesquiterpenes against the mosquito Aedes aegypti

Abstract

The Aedes aegypti mosquito serves as a major vector for viral diseases, such as dengue, chikungunya, and Zika, which are spreading across the globe and threatening public health. In addition to increased vector transmission, the prevalence of insecticide-resistant mosquitoes is also on the rise, thus solidifying the need for new, safe and effective insecticides to control mosquito populations. We recently discovered that cinnamodial, a unique drimane sesquiterpene dialdehyde of the Malagasy medicinal plant Cinnamosma fragrans, exhibited significant larval and adult toxicity to Ae. aegypti and was more efficacious than DEET-the gold standard for insect repellents-at repelling adult female Ae. aegypti from blood feeding. In this study several semi-synthetic analogues of cinnamodial were prepared to probe the structure-activity relationship (SAR) for larvicidal, adulticidal and antifeedant activity against Ae. aegypti. Initial efforts were focused on modification of the dialdehyde functionality to produce more stable active analogues and to understand the importance of the 1,4-dialdehyde and the α,ß-unsaturated carbonyl in the observed bioactivity of cinnamodial against mosquitoes. This study represents the first investigation into the SAR of cinnamodial as an insecticide and antifeedant against the medically important Ae. aegypti mosquito.

Natural Active Ingredients and TRPV1 Modulation: Focus on Key Chemical Moieties Involved in Ligand–Target Interaction

“…However, we must highlight the presence of numerous oxygen atoms which can behave like hydrogen bond acceptors. Furthermore, sesquiterpenes with an α,ß-unsaturated 1,4-dialdehyde moiety have been shown to undergo Paal–Knorr condensation reactions with lysine residues of TRP channels [ 180 ].…”

Evaluating the potential of environmentally friendly compounds to deactivate different life stages of Phytophthora species

“…Several synthetic polygodial analogues have been developed to improve the biological properties of polygodial. Most of these analogues have been designed by replacing the dialdehyde moiety of the drimane sesquiterpene scaffold with other reactive functional groups (Derita et al, 2013; Manwill et al, 2020). In our investigations, the reduced (Compound 4) and oxidized (Compound 5) forms of polygodial showed a 10‐fold reduction in antimycelial activity compared to polygodial itself.…”

“…Compound 5 (Manwill et al, 2020) Extracted polygodial (2.1 × 10 −4 mol, 50 mg) was dissolved in acetonitrile (2 mL). Sodium phosphate monobasic monohydrate (15 mg, 1.1 × 10 −4 mol) and 30% H 2 O 2 (22 μL, 9.4 × 10 −4 mol) dissolved in water (0.2 mL) was added to the above solution.…”

“…Polygodial is the most frequently identified sesquiterpene dialdehyde from horopito with noticeable biological activity (McCallion et al, 1982; Wayman et al, 2010). Synthetic derivatives of polygodial with known antifungal (Derita et al, 2013) and antifeedant (Manwill et al, 2020) activities have been reported in the literature. In this paper, we investigate the anti‐ Phytophthora activity of antifungal lipopeptides, polygodial and two synthetic derivatives (diol and dicarboxylic acid) of polygodial (Figure S1) against multiple life stages (mycelia, zoospores and oospores) of Phytophthora species.…”