Synthesis, insecticidal activities and resistance in Aedes albopictus and cytotoxicity of novel dihaloacetylated heterocyclic pyrethroids

Abstract

BACKGROUND: The use of safe and effective insecticides against mosquito-borne stocks is still one of the most effective ways to rapidly interrupt the spread of diseases such as malaria, dengue etc., but many insects are resistant to most insecticides and most of the traditional pyrethroids (like permethrin, deltamethrin etc.) contain phenoxy groups so it is easy to form dibenzofuran, a pollutant, after photodegradation. It is therefore necessary to synthesize novel pyrethroids which have better mosquito-killing activity, poor resistance to mosquitoes, and no dibenzofuran formation during photodegradation. RESULTS: A series of novel dihaloacetylated heterocyclic pyrethroids were synthesized to enhance antimosquito activity. Bioassays based on the guidelines of the Chinese Center for Disease Control and Prevention (CDC) indicate that the synthesized compounds DCA-O (LC 50 = 2.95 ± 0.05 g L −1 ), DCA-01 (LC 50 = 5.83 ± 0.36 g L −1 ) and DCA-11 (LC 50 = 5.79 ± 1.51 g L −1 ) exhibit high insecticidal activities and sensitivity against Aedes albopictus while deltamethrin and permethrin produced moderate levels of resistance. Moreover, the analysis of the photodegradation implies that the novel compounds synthesized by substituting a phenoxy group with a heterocyclic ring do not form dibenzofuran, a pollutant. Lastly, the cytotoxicity data of pyrethroids on human dopaminergic neuroblastoma SH-SY5Y cells confirm that the synthesized compounds have low toxicity for the cells. CONCLUSION: Novel dihaloacetylated heterocyclic pyrethroids, made by simple synthesis steps, have better antimosquito activity, lower drug resistance, are less polluting to the environment and show low toxicity to human nerve cells. This also provides an effective idea for the synthesis of pyrethroids. Novel dihaloacetylated heterocyclic pyrethroids have better antimosquito activity, lower drug resistance, are less polluting to the environment, ahow low toxicity to human nerve cells and simple synthesis steps.

Acute and chronic toxicity of deltamethrin, permethrin, and dihaloacetylated heterocyclic pyrethroids in mice

“…This signified that deltamethrin underwent a certain degree of metabolism or excretion in mice, but the bioaccumulation remained. When taking a single high dose, most deltamethrin could be metabolized or excreted, and produced a very low fraction of bioaccumulation, while when taking lower doses daily, most of the deltamethrin could accumulate in the body, and to a certain extent, cause poisoning or even death 13,25,39–43 …”

“…Deltamethrin (analytical standard, 95%) was purchased from Dr Ehrenstorfer GmbH (Augsburg, Germany). The synthesis and purification of dihaloacetylated heterocyclic pyrethroids DCA‐O, DCA‐01, and DCA‐11 are described previously (95%, racemate) 25 . The structures and mosquitoes‐killing activities against Aedes albopictus of the analytes are shown in Table 1.…”

“…Toxic ratio is defined as the ratio of permethrin's LC 50 value for baseline toxicity and the compounds' LC 50 values. This table is taken from Zhu et al 25 …”

“…The synthesis and purification of dihaloacetylated heterocyclic pyrethroids DCA-O, DCA-01, and DCA-11 are described previously (95%, racemate). 25 The structures and mosquitoes-killing activities against Aedes albopictus of the analytes are shown in Table 1. Glutamate (Glu, 98%), homoserine (IS, 99%) were provided by the National Standard Material Center (Beijing, China) and the Alfa Aesar Chemical Co. Ltd (Shanghai, China), respectively.…”

“…When taking a single high dose, most deltamethrin could be metabolized or excreted, and produced a very low fraction of bioaccumulation, while when taking lower doses daily, most of the deltamethrin could accumulate in the body, and to a certain extent, cause poisoning or even death. 13,25,[39][40][41][42][43] Kaneko 13 showed that oral absorption of pyrethroids in rats and mice was high. In general, pyrethroids and their metabolites were rapidly and completely excreted into the urine and feces within a few days after oral administration, and did not accumulate in any particular tissue or organ.…”