Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity
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 eth...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/11/3350 |
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| author | Nazlı Turan Yücel Derya Osmaniye Ümmühan Kandemir Asaf Evrim Evren Özgür Devrim Can Ümide Demir Özkay |
| author_facet | Nazlı Turan Yücel Derya Osmaniye Ümmühan Kandemir Asaf Evrim Evren Özgür Devrim Can Ümide Demir Özkay |
| author_sort | Nazlı Turan Yücel |
| collection | DOAJ |
| description | 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, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds <b>3a</b>–<b>3c</b>, <b>3f</b>, and <b>3g</b> (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 <b>3a</b>–<b>3c</b>, <b>3f</b>, and <b>3g</b>, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-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. |
| first_indexed | 2024-03-10T10:47:12Z |
| format | Article |
| id | doaj.art-c9d805244984453e9ac919ac1bdf305f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:47:12Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c9d805244984453e9ac919ac1bdf305f2023-11-21T22:32:35ZengMDPI AGMolecules1420-30492021-06-012611335010.3390/molecules26113350Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the ActivityNazlı Turan Yücel0Derya Osmaniye1Ümmühan Kandemir2Asaf Evrim Evren3Özgür Devrim Can4Ümide Demir Özkay5Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Eskişehir 26470, TurkeyFaculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, Eskişehir 26470, TurkeyInstitute of Health Sciences, Department of Pharmacology, Anadolu University, Eskişehir 26470, TurkeyVocational School of Health Services, Pharmacy Services, Bilecik Şeyh Edebali University, Bilecik 11230, TurkeyFaculty of Pharmacy, Department of Pharmacology, Anadolu University, Eskişehir 26470, TurkeyFaculty of Pharmacy, Department of Pharmacology, Anadolu University, Eskişehir 26470, TurkeyIn 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, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds <b>3a</b>–<b>3c</b>, <b>3f</b>, and <b>3g</b> (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 <b>3a</b>–<b>3c</b>, <b>3f</b>, and <b>3g</b>, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-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.https://www.mdpi.com/1420-3049/26/11/3350thiazolepiperazinetail-cliphot-plateacetic acid-induced writhing testopioid |
| spellingShingle | Nazlı Turan Yücel Derya Osmaniye Ümmühan Kandemir Asaf Evrim Evren Özgür Devrim Can Ümide Demir Özkay Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity Molecules thiazole piperazine tail-clip hot-plate acetic acid-induced writhing test opioid |
| title | Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity |
| title_full | Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity |
| title_fullStr | Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity |
| title_full_unstemmed | Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity |
| title_short | Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity |
| title_sort | synthesis and antinociceptive effect of some thiazole piperazine derivatives involvement of opioidergic system in the activity |
| topic | thiazole piperazine tail-clip hot-plate acetic acid-induced writhing test opioid |
| url | https://www.mdpi.com/1420-3049/26/11/3350 |
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