{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:05:34Z","timestamp":1774893934939,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a\u20133c, 3f, and 3g (50 mg\/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a\u20133c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and \u00b5- and \u03b4-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.<\/jats:p>","DOI":"10.3390\/molecules26113350","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T10:38:39Z","timestamp":1622630319000},"page":"3350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-2703","authenticated-orcid":false,"given":"Nazl\u0131 Turan","family":"Y\u00fccel","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-436X","authenticated-orcid":false,"given":"Derya","family":"Osmaniye","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3314-1961","authenticated-orcid":false,"given":"\u00dcmm\u00fchan","family":"Kandemir","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Department of Pharmacology, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asaf Evrim","family":"Evren","sequence":"additional","affiliation":[{"name":"Vocational School of Health Services, Pharmacy Services, Bilecik \u015eeyh Edebali University, Bilecik 11230, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zg\u00fcr Devrim","family":"Can","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00dcmide","family":"Demir \u00d6zkay","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Eski\u015fehir 26470, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cvsm.2019.07.005","article-title":"Adjuvant Analgesics in Acute Pain Management","volume":"49","author":"Ruel","year":"2019","journal-title":"Vet. 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