{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:27:48Z","timestamp":1787506068058,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pest Management Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Natural products are important sources of insecticidal lead compounds and are central to the development of green pesticides. Arecoline, the primary alkaloid in betel nut, shows insecticidal activity against\n                      <jats:italic>Aedes aegypti<\/jats:italic>\n                      . This study aimed to synthesize arecoline benzyl ester derivatives with improved activity and to investigate how they act by interfering with hormone signaling pathways and chitin metabolism in\n                      <jats:italic>Ae. aegypti<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      This study synthesized 22 arecoline benzyl ester derivatives and evaluated for insecticidal activity against fourth\u2010instar\n                      <jats:italic>Ae. aegypti<\/jats:italic>\n                      larvae. Among these, compound\n                      <jats:bold>4r<\/jats:bold>\n                      (3\u2010phenoxy) exhibited the highest potency (median lethal concentration (LC\n                      <jats:sub>50<\/jats:sub>\n                      )\u2009=\u200964.21\u2009mg\/L), significantly surpassing arecoline (LC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u2009100.82\u2009mg\/L). Mechanistic studies indicate that compound\n                      <jats:bold>4r<\/jats:bold>\n                      significantly reduces 20\u2010hydroxyecdysone (20E) levels in larvae, down\u2010regulated the expression of the early\u2010late transcription factor\n                      <jats:italic>Hr3<\/jats:italic>\n                      induced by ecdysone receptor (EcR) and ultraspiracle (USP), thereby disrupting the 20E\u2010\n                      <jats:italic>EcR\/USP<\/jats:italic>\n                      \u2010\n                      <jats:italic>Hr3<\/jats:italic>\n                      hormonal signaling axis. This, in turn, suppressed key downstream chitin\u2010metabolism genes, including\n                      <jats:italic>CHS\u20102<\/jats:italic>\n                      ,\n                      <jats:italic>CHT10<\/jats:italic>\n                      and\n                      <jats:italic>CHIA<\/jats:italic>\n                      , reduced chitinase activity and total chitin content, and ultimately led to disruption of chitin homeostasis and blockage of normal larval development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Arecoline benzyl ester\n                      <jats:bold>4r<\/jats:bold>\n                      is a promising insecticidal lead that perturbs 20E signaling via EcR\/USP and\n                      <jats:italic>Hr3<\/jats:italic>\n                      and dysregulates downstream chitin synthase and chitinase genes, thereby disrupting chitin homeostasis and larval development in\n                      <jats:italic>Ae. aegypti<\/jats:italic>\n                      . These findings provide a scientific basis for further optimization of arecoline\u2010based mosquito control agents targeting the chitin pathway. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.70536","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:52:31Z","timestamp":1768207951000},"page":"4239-4250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis of arecoline benzyl ester derivatives and investigation of insecticidal mechanism against\n                    <scp>\n                      <i>Aedes aegypti<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"82","author":[{"given":"Fei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Tropical Agriculture and Forestry Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxiang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Tropical Agriculture and Forestry Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Tropical Agriculture and Forestry Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Tropical Agriculture and Forestry Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Tropical Agriculture and Forestry Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-4291","authenticated-orcid":false,"given":"Yanping","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Tropical Agriculture and Forestry Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aac.2023.09.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.70092"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aac.2023.05.003"},{"key":"e_1_2_9_6_1","unstructured":"KnoxLH Production of Arecoline. US Patent(1950)."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0260281"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sajb.2022.11.028"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.1978.tb02449.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2024.106044"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42690-022-00866-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2021.109490"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c08643"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.181.1.257"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1964.tb07529.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00711"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24194"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.07.017"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2023.104058"},{"key":"e_1_2_9_20_1","first-page":"437","volume-title":"Adv Insect Physiol","author":"Doucet D","year":"2012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.8758"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2024.114373"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-024-11102-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.7b04130"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.6313"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.7840"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c01033"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0048-3575(85)90092-6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-60053-2"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c12401"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2025.110626"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c07237"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2024.112893"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-019-3867-z"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-021-04741-2"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2022.105221"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscombsci.8b00002"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00228"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c06516"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13321-017-0247-6"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.56.227"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2024.104071"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.135937"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/icb\/icad077"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2022.106378"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2017.11.001"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2014.942250"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2017.06.007"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2009.04.235"}],"container-title":["Pest Management Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ps.70536","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ps.70536","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ps.70536","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:53:26Z","timestamp":1776056006000},"score":1,"resource":{"primary":{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/10.1002\/ps.70536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ps.70536"],"URL":"https:\/\/doi.org\/10.1002\/ps.70536","archive":["Portico"],"relation":{},"ISSN":["1526-498X","1526-4998"],"issn-type":[{"value":"1526-498X","type":"print"},{"value":"1526-4998","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"assertion":[{"value":"2025-10-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}