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Among them, anxiety is among the top ten diseases and causes an annual cost of 42.3 billion dollars in the United States. It can also increase the chance of developing diabetes, regardless of cardiometabolic and sociodemographic factors. Diabetes, if left uncontrolled for long periods, can lead to serious health problems and, in 2021, was responsible for the deaths of 1.6 million people and affected around 10.5% of the world population. chalcones belong to the class of flavonoid compounds and have gained prominence in recent years for presenting a wide range of physiological effects, with similar effects also being found in the literature when these compounds are synthesized. Therefore, the work aimed at the synthesis, characterization, toxicological, anxiolytic, hypoglycemic, and anticonvulsant analysis of the compound 4AAF in Danio rerio. Initially, amino chalcone was synthesized employing the Claisen\u2013Schmidt condensation reaction, and then its toxicity was tested over 96 h at concentrations of 0.1, 0.5, and 1.0 mg\/mL. Subsequently, groups of 6 treated animals were formed to evaluate their effects in the following tests: light and dark, novel tank test, open field test, spinning task, anxiolytic action mechanism via GABA and serotonergic, chronic hyperglycemia, reactive oxygen species, and pentylenetetrazol-induced seizure. The compound produced was shown to be nontoxic, and anxiety tests were promising at concentrations of 0.5 mg\/mL, showing that aminochalcone acts on both the GABA and serotonergic pathways and that it causes a reduction in the locomotor pattern of the animals. In the context of hyperglycemia, the concentration of 0.5 mg\/mL significantly reduced blood glucose levels and oxidative stress in the liver, in addition to causing anxiolytic and sedative behavior. In the seizure test, the 1.0 mg\/mL concentration partially reversed PTZ-induced convulsive behavior in stage three. Finally, synthetic chalcones have more than one physiological effect, requiring bioprospecting for other possible actions, and zebrafish become an interesting model to investigate their various uses.<\/jats:p>","DOI":"10.1021\/acsomega.5c01614","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T04:33:37Z","timestamp":1752467617000},"page":"30313-30326","source":"Crossref","is-referenced-by-count":1,"title":["Synthetic Aminochalcone\nPrevents Hyperglycemia-Induced\nAnxiety and Delays Pentylenetetrazole-Induced Epileptic Crisis in\nAdult Zebrafish"],"prefix":"10.1021","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7912-7394","authenticated-orcid":true,"given":"Arnaldo\nSolheiro","family":"Bezerra","sequence":"first","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amauri Barbosa","family":"da Silva Junior","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Wlisses","family":"da Silva","sequence":"additional","affiliation":[{"name":"Chemical-pharmacological and Environmental Bioassay Laboratory - LABQFAM , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela de Lima","family":"Rebouc\u0327as Borges","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levi Magalha\u0303es Gurgel","family":"Mace\u0302do","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yago Kayan de Souza","family":"Lima","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Costa","family":"de Sousa","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Helena Gama","family":"Joca","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Lorena Pereira","family":"Bezerra","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick Patrick\nAlves","family":"Moreira","sequence":"additional","affiliation":[{"name":"Mauricio de Nassau University Center , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u0301cia de Fa\u0301tima Mota","family":"Pernambuco","sequence":"additional","affiliation":[{"name":"Mauricio de Nassau University Center , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Vito\u0301ria\nSantana","family":"Garcia","sequence":"additional","affiliation":[{"name":"Mauricio de Nassau University Center , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0301rcia Machado","family":"Marinho","sequence":"additional","affiliation":[{"name":"State University of Acarau\u0301 Valley , , , ,","place":["Sobral, Ceara, Brazil, 62010-295"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Silva Marinho","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damia\u0303o\nSampaio","family":"de Sousa","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Nogueira","family":"Bandeira","sequence":"additional","affiliation":[{"name":"State University of Acarau\u0301 Valley , , , ,","place":["Sobral, Ceara, Brazil, 62010-295"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Ferdinando\nMesquita","family":"Cajazeiras","sequence":"additional","affiliation":[{"name":"State University of Acarau\u0301 Valley , , , ,","place":["Sobral, Ceara, Brazil, 62010-295"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u0301lcio\nSilva dos","family":"Santos","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]},{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]},{"name":"State University of Acarau\u0301 Valley , , , ,","place":["Sobral, Ceara, Brazil, 62010-295"]},{"name":"Federal University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4569-8663","authenticated-orcid":true,"given":"Maria Izabel Florindo","family":"Guedes","sequence":"additional","affiliation":[{"name":"State University of Ceara , , , ,","place":["Fortaleza, Ceara, Brazil, 60714-903"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"2026081812212427000_cit1","doi-asserted-by":"publisher","DOI":"10.1017\/S2045796021000275","article-title":"Global, regional and national burden\nof anxiety disorders from 1990 to 2019: results from the Global Burden\nof Disease Study 2019","volume":"30","author":"Yang","year":"2021","journal-title":"Epidemiol Psychiatr Sci."},{"key":"2026081812212427000_cit2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113664","article-title":"Pharmacological insights\non the antidepressant, anxiolytic\nand aphrodisiac potentials of Aglaonema hookerianum Schott","volume":"268","author":"Goni","year":"2021","journal-title":"Journal of Ethnopharmacology"},{"key":"2026081812212427000_cit3","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1590\/1516-4446-2019-0830","article-title":"Benzodiazepine\nconsumption in Brazil: considerations 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Psychiatry"},{"key":"2026081812212427000_cit4","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.psc.2009.05.004","article-title":"The Neurobiology\nof Anxiety Disorders: Brain Imaging, Genetics, and Psychoneuroendocrinology","volume":"32","author":"Martin","year":"2009","journal-title":"Psychiatric Clinics of North America"},{"key":"2026081812212427000_cit5","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00213-007-0890-0","article-title":"anxiolytic effects\ninduced by inhibition of the nitric\noxide\u2013cGMP pathway in the rat dorsal hippocampus","volume":"195","author":"Spolido\u0301rio","year":"2007","journal-title":"Psychopharmacology"},{"key":"2026081812212427000_cit6","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.3390\/molecules25122907","article-title":"The Antioxidant,\nAnti-Inflammatory, and Neuroprotective Properties of the Synthetic\nchalcone Derivative AN07","volume":"25","author":"Chen","year":"2020","journal-title":"Molecules"},{"key":"2026081812212427000_cit7","first-page":"214","article-title":"Benzodiazepine Pharmacology\nand Central Nervous System\u2013Mediated Effects","volume":"13","author":"Griffin","year":"2013","journal-title":"Ochsner J."},{"key":"2026081812212427000_cit8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainresbull.2014.03.002","article-title":"Duration of treatment and activation\nof \u03b11-containing GABAA receptors variably affect the level of\nanxiety and seizure susceptibility after diazepam withdrawal in rats","volume":"104","author":"Kovac\u030cevic\u0301","year":"2014","journal-title":"Brain Res. Bull."},{"key":"2026081812212427000_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.112518","article-title":"anxiolytic-like\neffects of the ethanol extract of Magnolia\nobovata leaves through its effects on GABA-benzodiazepine receptor\nand neuroinflammation","volume":"383","author":"Ham","year":"2020","journal-title":"Behavioural Brain Research"},{"key":"2026081812212427000_cit10","doi-asserted-by":"publisher","first-page":"41","DOI":"10.4103\/1673-5374.264445","article-title":"Selective\nserotonin reuptake inhibitors\nand Alzheimer\u2019s disease","volume":"15","author":"Mdawar","year":"2020","journal-title":"Neural Regen\nRes."},{"key":"2026081812212427000_cit11","doi-asserted-by":"publisher","first-page":"14021","DOI":"10.33263\/BRIAC116.1402114031","article-title":"anxiolytic-like\nand Anticonvulsant Effect in Adult Zebrafish (Danio rerio) through\nGABAergic System and Molecular Docking Study of chalcone Derived from\nNatural Products","volume":"11","author":"Xavier","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"2026081812212427000_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111973","article-title":"An aqueous\nextract of Canarium schweinfurthii attenuates seizures and potentiates\nsleep in mice: Evidence for involvement of GABA Pathway","volume":"142","author":"Kandeda","year":"2021","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"2026081812212427000_cit13","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.2174\/156802611795371350","article-title":"GABAA receptor\nsubtype-selective modulators. I. \u03b12\/\u03b13-Selective Agonists\nas Non-Sedating Anxiolytics","volume":"11","author":"Atack","year":"2011","journal-title":"Curr. Top. Med.\nChem."},{"key":"2026081812212427000_cit14","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.bbr.2013.12.007","article-title":"Differential\nrole of the basolateral\namygdala 5-HT3 and 5-HT4 serotonin receptors upon ACPA-induced anxiolytic-like\nbehaviors and emotional memory deficit in mice","volume":"261","author":"Chegini","year":"2014","journal-title":"Behavioural Brain Research"},{"key":"2026081812212427000_cit15","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/dme.13606","article-title":"Investigating the longitudinal\nassociation\nbetween diabetes and anxiety: a systematic review and meta-analysis","volume":"35","author":"Smith","year":"2018","journal-title":"Diabet. Med."},{"key":"2026081812212427000_cit16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2022.110991","article-title":"A bidirectional\nrelationship between diabetes mellitus and anxiety: A systematic review\nand meta-analysis","volume":"162","author":"Mersha","year":"2022","journal-title":"Journal of Psychosomatic\nResearch"},{"key":"2026081812212427000_cit17","unstructured":"World Health Organization\n          . Diabetes. 2023. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/diabetes."},{"key":"2026081812212427000_cit18","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1007\/s10792-020-01448-8","article-title":"Natural\nhistory and visual outcome of nonarteritic anterior ischemic optic\nneuropathy in Southern Taiwan: a pilot study","volume":"40","author":"Huang","year":"2020","journal-title":"Int. Ophthalmol"},{"key":"2026081812212427000_cit19","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1556\/oh.2008.28406","article-title":"The serotonin\ntransporter gene and personality: association of the 5-HTTLPR s allele,\nanxiety, depression and affective temperaments","volume":"149","author":"Gonda","year":"2008","journal-title":"Orvosi Hetilap"},{"key":"2026081812212427000_cit20","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1556\/650.2021.32169","article-title":"A szoronga\u0301s\ne\u0301s a diabetes ko\u0308zti kapcsolat","volume":"162","author":"Hargittay","year":"2021","journal-title":"Orv Hetil."},{"key":"2026081812212427000_cit21","doi-asserted-by":"publisher","first-page":"8307","DOI":"10.1038\/s41598-020-57647-x","article-title":"Anxiety and depression\nin diabetes care: longitudinal associations with health-related quality\nof life","volume":"10","author":"Liu","year":"2020","journal-title":"Sci. Rep"},{"key":"2026081812212427000_cit22","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1517\/13543776.14.12.1669","article-title":"Recent advances in therapeutic chalcones","volume":"14","author":"Ni","year":"2004","journal-title":"Expert Opinion on Therapeutic Patents"},{"key":"2026081812212427000_cit23","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1021\/cc000075z","article-title":"Linked Parallel\nSynthesis and MTT\nBioassay Screening of Substituted chalcones","volume":"3","author":"Lawrence","year":"2001","journal-title":"J. Comb. Chem."},{"key":"2026081812212427000_cit24","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1016\/j.ejmech.2008.05.010","article-title":"Examination of growth inhibitory\nproperties of synthetic chalcones for which antibacterial activity\nwas predicted","volume":"44","author":"Batovska","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"2026081812212427000_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.132064","article-title":"Structural and spectroscopic analysis,\nADMET study, and anxiolytic-like effect in adult zebrafish (Danio\nrerio) of 4\u2032-[(1E,2E)-1-(2-(2\u2032,4\u2032-dinitrophenyl)\u00adhydrazone-3-(4-methoxyphenyl)\u00adallyl)\u00adaniline","volume":"1251","author":"De\nSouza","year":"2022","journal-title":"J. Mol. Struct."},{"key":"2026081812212427000_cit26","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.bbrc.2020.03.129","article-title":"anxiolytic-like effect of chalcone N-{4\u2019[(2E)-3-(3-nitrophenyl)-1-(phenyl)\u00adprop-2-en-1-one]}\nacetamide on adult zebrafish (Danio rerio): Involvement of the 5-HT\nsystem","volume":"526","author":"Ferreira","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026081812212427000_cit27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.33263\/BRIAC131.015","article-title":"Jane Eire Silva\nAlencar de Menezes, Paulo Nogueira Bandeira, Alexandre Magno Rodrigues\nTeixeira, Emanuelle Machado Marinho, Ma\u0301rcia Machado Marinho,\nEmmanuel Silva Marinho, He\u0301lcio Silva dos Santos, anxiolytic-like\nEffect in Adult Zebrafish (Danio rerio) through GABAergic System and\nMolecular Docking Study of chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)\u00adprop-2-en-1-one","volume":"13","author":"Guedes","year":"2022","journal-title":"Biointerface Res. Appl. 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Rep"},{"key":"2026081812212427000_cit34","doi-asserted-by":"publisher","first-page":"7374","DOI":"10.3390\/molecules27217374","article-title":"Zebrafish:\nA Pharmacological\nModel for Learning and Memory Research","volume":"27","author":"Tan","year":"2022","journal-title":"Molecules"},{"key":"2026081812212427000_cit35","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1007\/s00210-021-02116-z","article-title":"anxiolytic-like\neffect of natural product 2-hydroxy-3,4,6-trimethoxyacetophenone isolated\nfrom Croton anisodontus in adult zebrafish via serotonergic neuromodulation\ninvolvement of the 5-HT system","volume":"394","author":"Da\nSilva","year":"2021","journal-title":"Naunyn-Schmiedeberg\u2019s\nArch. Pharmacol."},{"key":"2026081812212427000_cit36","doi-asserted-by":"publisher","first-page":"12426","DOI":"10.1080\/07391102.2023.2167116","article-title":"GABA A and serotonergic\nreceptors participation in anxiolytic effect of chalcones in adult\nzebrafish","volume":"41","author":"Mendes","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2026081812212427000_cit37","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3389\/fcell.2018.00091","article-title":"Zebrafish\nas a Model for Obesity\nand Diabetes","volume":"6","author":"Zang","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"2026081812212427000_cit38","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.cbpb.2014.03.005","article-title":"Persistent impaired\nglucose metabolism in a zebrafish\nhyperglycemia model","volume":"171","author":"Capiotti","year":"2014","journal-title":"Comp. Biochem. Physiol."},{"key":"2026081812212427000_cit39","doi-asserted-by":"publisher","DOI":"10.1016\/j.endmts.2020.100058","article-title":"Study of learning\nand memory in type 2 diabetic model\nof zebrafish (Danio rerio)","volume":"1","author":"Ranjan","year":"2020","journal-title":"Endocr. Metab. 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