Larvicidal formulation containing N-tosylindole: A viable alternative to chemical control of Aedes aegypti.

Aedes aegypti is currently a major public health problem. This mosquito is responsible for the spread of infectious diseases that have been causing epidemics worldwide. Surfactant-stabilized systems, such as microemulsions, liquid-crystalline precursors and liquid crystals, are promising sustained delivery formulations of hydrophilic and hydrophobic substances. These systems are biocompatible water-soluble reservoirs for N-tosylindole exhibiting biological activity against Aedes aegypti Linn. (Diptera: Culicidae) larvae. The ternary diagram displayed four regions: microemulsion (ME), liquid crystal (LC), emulsion (EM) and phase separation (PS). PLM and SAXS distinguished microemulsions, lamellar and hexagonal phase liquid crystals. The system had a lethal concentration of 50% (LC50 = 0.1 ppm, 0.36 µM) lower than pure N-tosylindole (0.24 ppm, 0.88 µM), which has limitations in aqueous media. Furthermore, the formulation displayed no toxicity to Artemia sp., a non-target organism. The system exhibited excellent larvicidal activity as an alternative to commercial larvicides that have shown resistance and toxicity to the environment by Ae. aegypti larvae due to prolonged use. In addition, a two-fold increase in potency was observed.

Synthesis and Chemometrics of Thymol and Carvacrol Derivatives as Larvicides against Aedes aegypti.

BACKGROUND: Thymol and carvacrol have previously demonstrated larvicidal activity against Aedes aegypti (Diptera: Culicidae). In view of this fact, it was of our interest to obtain synthetic derivatives and evaluate their larvicidal activity on Ae. aegypti larvae. METHODS: Structural modifications were performed on thymol and carvacrol in an effort to understand the functional groups necessary for modulating their activities and to lead possibly to more effective larvae control agents. The derivatives were further subjected to SAR and computational studies (molecular modeling and chemometric tools (CPCA and PCA)) to extract structural information regarding their larvicidal properties. Field collected and Rockefeller populations of Ae. aegypti were used. RESULTS: Carvacrol and thymol exhibited LC50 of 51 and 58ppm for field collected larvae, respectively. Carvacrol derivatives exhibited LC50 ranging from 39 to 169ppm, while thymol derivatives exhibited LC50 ranging from 18 to 465ppm. Substitution of the acidic proton of carvacrol by esters, ethers, and acetic acid resulted in either maintenance or reduction of potency. CONCLUSION: Thymol derivatives were, to a certain extent, more efficient larvicides against Ae. aegypti than carvacrol derivatives, particularly to Rockefeller larvae. The chemometrics tools applied in this study showed that the independent variables indicate a mixed profile. Nevertheless, hydrophobic interactions increased the larvicidal activity.

Synthesis and pharmacological evaluation of carvacrol propionate.

This study aimed at synthesizing the carvacrol propionate (CP) and evaluating its pharmacological profile. CP was obtained from carvacrol and propionyl chloride through an esterification reaction. Male Swiss mice were treated with CP (25, 50, or 100 mg/kg). We evaluated the analgesic effect, mechanical hyperalgesia, and anti-inflammatory effect. Pre-treatment with CP inhibited (p<0.01 and 0.001) the formalin-induced nociception in both phases. CP inhibited (p<0.05, 0.01, and 0.001) the development of mechanical hyperalgesia. CP was able to decrease the leukocyte recruitment (p<0.001) and the amount of TNF-α (p<0.001), IL-1ß (p<0.05), and protein leakage (p<0.01) into the pleural cavity. In addition, the paw edema was inhibited by CP (p<0.05, 0.01, and 0.001). The CP attenuates nociception, mechanical hyperalgesia, and inflammation, through an inhibition of cytokines.