Cardol-Derived Organophosphorothioates as Inhibitors of Acetylcholinesterase for Dengue Vector Control

Mayara Almeida,Maria Trevisan,Nayane Lima,Thayllan Bezerra,Anderson Sousa,Selma Mazzetto,Viviane Ribeiro,Diego Lomonaco

doi:10.21577/0103-5053.20190181

Abstract

Aedes aegypti is the main vector of three neglected tropical diseases: dengue, zika and chikungunya. Dengue is under surveillance by health organizations worldwide due to the risk of epidemics. Since there is no specific treatment for dengue, most studies have focused on preventing the reproduction and/or development of the mosquitoes. We studied the larvicidal activity of five phosphates and phosphorothioates derived from cardol, one of the four main components of cashew nut shell liquid (Anacardium occidentale L.), at different concentrations. The organophosphorothioate derivatives were tested for their in vitro inhibitory potential against acetylcholinesterase (AChE). One compound, Cdl.i-dPS (median lethal concentration (LC50) = 0.8 ppm), was four times more efficient compared to an important commercial larvicide, Temephos (LC50 = 3.2 ppm), and showed greater AChE inhibition than its monosubstituted analogue and Temephos.

Highlights

The female Aedes aegypti mosquito is the main arbovirus vector responsible for three neglected tropical diseases (NTDs): dengue, chikungunya and zika
Previous works[13] have used cardol, a natural phenol obtained from cashew nut shell liquid (CNSL), which presented good larvicidal activity
The larvicidal activity of organophosphorothioates against Aedes aegypti can be attributed to inhibition of the enzyme acetylcholinesterase (AChE)

Summary

Introduction

The female Aedes aegypti mosquito is the main arbovirus vector responsible for three neglected tropical diseases (NTDs): dengue, chikungunya and zika. We published a study[13] on CNSL constituents larvicidal activity, and cardol exhibited the best results Aiming to improve this activity and inspired by the structure of commercial organophosphorus larvicides, in this work we synthesized phosphate and phosphorothioate derivatives of cardol and evaluated their efficiency and mode of action as larvicides and acetylcholinesterase (AChE) inhibitors of Aedes aegypti, for vector control in still water. Diagram of the synthesis of the organophosphate larvicides from cardol This period, brine (40 mL) was added and the resultant solution was extracted with ethyl acetate (3 × 40 mL). The value of LC50 was determined using the statistical analysis software BioStat 2009.20 This assay was performed according to the method described by Elmann, with adaptations.[21,22] Aliquots of 15 μL of solutions of 2, 4 and commercial larvicide (Temephos), with concentration of 0.45 mg mL-1, were spotted on a TLC plate (DC-Alufolien, Silicagel 60 F254, 0.2 mm Merck). An anticholinesterase compound called Eserin was used at 30 mg mL-1

Results and Discussion

Result

Conclusions