Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors
μ-opioid receptor ligands such as morphine and fentanyl are the most known and potent painkillers. However, the severe side effects seen with their use significantly limit their widespread use. The continuous broadening of knowledge about the properties of the interactions of the MOP receptor (human...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/3/571 |
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| author | Dominik Straszak Sylwia Woźniak Agata Siwek Monika Głuch-Lutwin Marcin Kołaczkowski Aldona Pietrzak Bartłomiej Drop Dariusz Matosiuk |
| author_facet | Dominik Straszak Sylwia Woźniak Agata Siwek Monika Głuch-Lutwin Marcin Kołaczkowski Aldona Pietrzak Bartłomiej Drop Dariusz Matosiuk |
| author_sort | Dominik Straszak |
| collection | DOAJ |
| description | μ-opioid receptor ligands such as morphine and fentanyl are the most known and potent painkillers. However, the severe side effects seen with their use significantly limit their widespread use. The continuous broadening of knowledge about the properties of the interactions of the MOP receptor (human mu opioid receptor, OP3) with ligands and specific intracellular signaling pathways allows for the designation of new directions of research with respect to compounds with analgesic effects in a mechanism different from classical ligands. Allosteric modulation is an extremely promising line of research. Compounds with modulator properties may provide a safer alternative to the currently used opioids. The aim of our research was to obtain a series of urea derivatives of 1-aryl-2-aminoimidazoline and to determine their activity, mechanism of biological action and selectivity toward the MOP receptor. The obtained compounds were subjected to functional tests (cAMP accumulation and β-arrestin recruitment) in vitro. One of the obtained compounds, when administered alone, did not show any biological activity, while when co-administered with DAMGO, it inhibited β-arrestin recruitment. These results indicate that this compound is a negative allosteric modulator (NAM) of the human MOP receptor. |
| first_indexed | 2024-03-08T03:52:30Z |
| format | Article |
| id | doaj.art-320eb04a4c514654807a191ca7115d2e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T03:52:30Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-320eb04a4c514654807a191ca7115d2e2024-02-09T15:18:40ZengMDPI AGMolecules1420-30492024-01-0129357110.3390/molecules29030571Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP ReceptorsDominik Straszak0Sylwia Woźniak1Agata Siwek2Monika Głuch-Lutwin3Marcin Kołaczkowski4Aldona Pietrzak5Bartłomiej Drop6Dariusz Matosiuk7Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University, Chodzki 4A, 20-093 Lublin, PolandDepartment of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University, Chodzki 4A, 20-093 Lublin, PolandFaculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandFaculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandFaculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, PolandDepartment of Dermatology, Venereology, and Paediatric Dermatology, Faculty of Medicine, Medical University, Staszica 11, 20-080 Lublin, PolandDepartment of Medical Informatics and Statistics, Medical University, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University, Chodzki 4A, 20-093 Lublin, Polandμ-opioid receptor ligands such as morphine and fentanyl are the most known and potent painkillers. However, the severe side effects seen with their use significantly limit their widespread use. The continuous broadening of knowledge about the properties of the interactions of the MOP receptor (human mu opioid receptor, OP3) with ligands and specific intracellular signaling pathways allows for the designation of new directions of research with respect to compounds with analgesic effects in a mechanism different from classical ligands. Allosteric modulation is an extremely promising line of research. Compounds with modulator properties may provide a safer alternative to the currently used opioids. The aim of our research was to obtain a series of urea derivatives of 1-aryl-2-aminoimidazoline and to determine their activity, mechanism of biological action and selectivity toward the MOP receptor. The obtained compounds were subjected to functional tests (cAMP accumulation and β-arrestin recruitment) in vitro. One of the obtained compounds, when administered alone, did not show any biological activity, while when co-administered with DAMGO, it inhibited β-arrestin recruitment. These results indicate that this compound is a negative allosteric modulator (NAM) of the human MOP receptor.https://www.mdpi.com/1420-3049/29/3/571MOP receptorOP3 receptorallosterismβ-arrestin1-aryl-2-aminoimidazoline-2 |
| spellingShingle | Dominik Straszak Sylwia Woźniak Agata Siwek Monika Głuch-Lutwin Marcin Kołaczkowski Aldona Pietrzak Bartłomiej Drop Dariusz Matosiuk Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors Molecules MOP receptor OP3 receptor allosterism β-arrestin 1-aryl-2-aminoimidazoline-2 |
| title | Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors |
| title_full | Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors |
| title_fullStr | Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors |
| title_full_unstemmed | Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors |
| title_short | Novel 1-(1-Arylimiazolin-2-Yl)-3-Arylalkilurea Derivatives with Modulatory Activity on Opioid MOP Receptors |
| title_sort | novel 1 1 arylimiazolin 2 yl 3 arylalkilurea derivatives with modulatory activity on opioid mop receptors |
| topic | MOP receptor OP3 receptor allosterism β-arrestin 1-aryl-2-aminoimidazoline-2 |
| url | https://www.mdpi.com/1420-3049/29/3/571 |
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