ABSTRACT Synthetic chemical insecticides are widely used in population control of pests. Aedes aegypti is the primary vector of dengue, Zika, chikungunya and yellow fever to humans, and has proven resistance to chemical insecticides. As an alternative vector control method, the ethanolic extract of the leaves of Piper peltatum L. (Piperaceae) showed larvicidal activity against Ae. aegypti. Despite the wide medicinal use of this plant, the biological activity of its isolated constituents remains unexplored. In this sense, we isolated, identified and evaluated the larvicidal activity of 4-nerolidylcatechol (4-NC) from P. peltatum against Ae. aegypti, Culex quinquefasciatus and Anopheles darlingi, focusing on the larvicidal, adulticidal and genotoxic potential of 4-NC on Ae. aegypti. Larvae were captured in the city of Manaus, Amazonas state, Brazil. 4-NC was isolated from the extract of the leaves of P. peltatum via silica gel chromatography. This was identified using nuclear magnetic resonance spectroscopy and tested in Artemia franciscana (6.25, 12.5, 25, 50, 100 and 200 µg/mL). In the toxicity bioassay, Ae. aegypti larvae were exposed to 30, 50, 70, 90, and 110 µg/mL of 4-NC, while Cx. quinquefasciatus and An. darlingi were exposed to 6.25, 12.5, 25, 50 and 100 µg/mL. Ae. aegypti larvae were also subjected to 40 and 60 µg/mL of 4-NC (genotoxicity bioassay), and adult females to 62.5 to 1,000 µg/mL (adulticidal bioassay). The results of the 4-NC toxicity assays showed that there was 100% mortality in larvae of Ar. franciscana at the concentration of 200 µg/mL, with an LC50 of 8.0 μg/mL. In the larvae of Ae. aegypti, mortality was 100%, with an LC50 of 62 μg/mL. In larvae of Cx. quinquefasciatus, 97% mortality occurred, with an LC50 of 52.3 μg/mL, and in An. darlingi larvae there was an 83% mortality rate, with an LC50 of 55.8 μg/mL. In adults of Ae. aegypti, however, there was no adulticidal activity. In the larvae of Ae. aegypti, the genotoxic effect of 4-NC (40 and 60 µg/mL) showed significant frequency (p < 0.05) of cellular abnormalities (micronuclei, budding and nuclear bridges) of interphasic nuclei of neuroblasts and oocytes in relation to the negative control. This result may be associated with a decrease in oviposition of females, which was observed in two generations. We can confirm that 4-NC has larvicidal activity against Ae. aegypti, Cx. quinquefasciatus and An. darlingi. Although it does not present adulticidal activity in Ae. aegypti, it reduced the oviposition of females. Therefore, 4-NC seems to be a strong candidate for the development of an alternative method for the control of these mosquitoes in the immature phase. pests dengue Zika humans L Piperaceae (Piperaceae Ae plant unexplored sense 4nerolidylcatechol nerolidylcatechol 4 4NC NC (4-NC P Manaus state Brazil chromatography 625 6 25 (6.25 125 12 5 12.5 10 20 µgmL . µg mL bioassay 30 70 90 11 4NC, NC, Cx An 6.25 genotoxicity , bioassay) 62. 1000 1 000 1,00 bioassay. Ar LC LC5 80 8 0 8. μgmL μg μg/mL 97 occurred 523 52 3 52. 83 rate 558 55 55. however (4 p 0.05 005 05 micronuclei, micronuclei (micronuclei bridges generations Therefore phase 2 (6.2 12. 7 9 6.2 00 1,0 ( 0.0 (6. 6. 1, 0. (6

ABSTRACT The new molecules piperidyl dillapiole and propyl ether dillapiole were evaluated in Aedes aegypti as an alternative for the control of populations of this mosquito. A total of 1,690 samples, comprising 780 eggs, 780 larvae and 130 adults, were treated with both substances for 4 h, 24 h and 90 min, respectively. The dillapiole (80 µg/mL), temephos (0.012 µg/mL) as positive control, and the negative control (water + DMSO 0.05%). The 50% lethal concentrations (LC50) of propyl ether dillapiole and piperidyl dillapiole in eggs were 18.07 and 49.97 µg/mL and, in larvae, the LC50 of these substances were 29.15 and 72.93 µg/mL, which caused darkening of the cuticle and displacement of the head. In the adults, the LC50 of the two substances after 90 min was 148.25 and 263.26 µg/mL, respectively. The insertion of the propyl and piperidine radicals into the dillapiole molecule resulted in the substances propyl ether dillapiole and piperidyl dillapiole, both of which had a toxic effect on Ae. aegypti. However, propyl ether dillapiole, which has propylene in its side chain, showed greater ovicidal, larvicidal and adulticidal activity when compared to piperidyl dillapiole. These results are promising as an alternative form of control of Ae. aegypti, which is the primary vector of human arboviruses. mosquito 1690 1 690 1,69 samples 78 13 adults 2 9 respectively 80 (8 µgmL , µg mL 0.012 0012 0 012 (0.01 water 0.05%. 005 0.05% . 05 0.05%) 50 LC (LC50 1807 18 07 18.0 4997 49 97 49.9 LC5 2915 29 15 29.1 7293 72 93 72.9 head 14825 148 25 148.2 26326 263 26 263.2 Ae However chain ovicidal arboviruses 169 69 1,6 7 8 ( 0.01 001 01 (0.0 00 0.05 5 (LC5 180 18. 499 49. 291 29. 729 72. 1482 14 148. 2632 263. 16 6 1, 0.0 (0. (LC 0. (0