{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T16:28:52Z","timestamp":1767025732043,"version":"3.48.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["439303\/2018\u20104"],"award-info":[{"award-number":["439303\/2018\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The privileged structures, such as dihydropyridine, are present in bioactive compounds exhibiting biological activities by interacting with multiple pharmacological targets. The dihydropyridine\u2010containing compounds are usually related to the calcium channel\u2013blocking abilities in the treatment of cardiovascular diseases, such as nifedipine. Other pharmaceutical applications have been described for these compounds, being a starting point for the obtaining of new drug candidates. The privileged structures are usually related to nontoxic effects; however, other chemical groups of dihydropyridine\u2010containing compounds may result in impairment of the safety profile, such as nifedipine, described as teratogenic and embryotoxic\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here, we designed LQFM310 through the molecular hybridization strategy by incorporating the dimethyl 2,6\u2010dimethyl\u20101,4\u2010dihydropyridine\u20103,5\u2010dicarboxylate scaffold from nifedipine and butyl hydroxytoluene (BHT). As the phenolic hydroxyl from BHT is capable of conferring antioxidant activity, the electrochemical analysis was performed. In addition, the toxicological profile of LQFM310 was investigated by using the embryo\u2010larval stage of zebrafish (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Danio rerio<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) and compared to nifedipine. As a result, LQFM310 demonstrated the antioxidant potential and did not induce significant lethal or sublethal effects in the toxicological assay. However, nifedipine induced 100% mortality in embryos and larvae from 25\u2009\u03bcM for 96\u2009h post fertilization (hpf) and sublethal effects at 10\u2009\u03bcM. Therefore, LQFM310 demonstrated a safer profile than nifedipine in the zebrafish\u2010based toxicity model, identifying that the nitroaromatic scaffold may be responsible for the toxicity effect of nifedipine. Considering the presence of privileged structures as dihydropyridine, LQFM310 is a promising compound for investigation in pharmacology assays of several diseases.\n                  <\/jats:p>","DOI":"10.1002\/jat.4829","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T01:49:12Z","timestamp":1749520152000},"page":"2108-2116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicity Assessment of a Derivative Designed by Using the Privileged Structure Dihydropyridine: LQFM310, a Nifedipine Analog"],"prefix":"10.1002","volume":"45","author":[{"given":"Amanda\u00a0C.","family":"Silva","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal Pharmaceutical Chemistry (LQFM), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"},{"name":"Environmental Toxicology Research Laboratory (EnvTox), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-5354","authenticated-orcid":false,"given":"Michele\u00a0R.","family":"Machado","sequence":"additional","affiliation":[{"name":"Environmental Toxicology Research Laboratory (EnvTox), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-5429","authenticated-orcid":false,"given":"Gerlon\u00a0A.\u00a0R.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Faculty of Health Sciences University of Bras\u00edlia  Bras\u00edlia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gessyca\u00a0G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Environmental Toxicology Research Laboratory (EnvTox), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisele\u00a0A.\u00a0R.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Environmental Toxicology Research Laboratory (EnvTox), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-2980","authenticated-orcid":false,"given":"Luciano\u00a0M.","family":"Li\u00e3o","sequence":"additional","affiliation":[{"name":"Nuclear Magnetic Resonance Laboratory (LabRMN), Institute of Chemistry Federal University of Goi\u00e1s, Campus Samambaia  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9161-0127","authenticated-orcid":false,"given":"Eric\u00a0S.","family":"Gil","sequence":"additional","affiliation":[{"name":"School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Menegatti","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Pharmaceutical Chemistry (LQFM), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-201X","authenticated-orcid":false,"given":"Gloria\u00a0N.\u00a0S.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Pharmaceutical Chemistry (LQFM), School of Pharmacy Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"},{"name":"School of Pharmacy Federal University of Bahia, Campus Ondina  Salvador Bahia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"129","article-title":"Intera\u00e7\u00e3o Entre Antioxidantes Naturais e Esp\u00e9cies Reativas do Oxig\u00eanio nas Doen\u00e7as Cardiovasculares: Perspectivas Para a Contribui\u00e7\u00e3o do Alecrim (Rosmarinus officinalis L.)","volume":"35","author":"Afonso M. 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