New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy
The purpose of the present paper was to assess the ability of five newly designed and synthesized meloxicam analogues to interact with phospholipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of the chemical structure, the studied compou...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/13/4/416 |
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| author | Jadwiga Maniewska Justyna Gąsiorowska Żaneta Czyżnikowska Krystyna Michalak Berenika M. Szczęśniak-Sięga |
| author_facet | Jadwiga Maniewska Justyna Gąsiorowska Żaneta Czyżnikowska Krystyna Michalak Berenika M. Szczęśniak-Sięga |
| author_sort | Jadwiga Maniewska |
| collection | DOAJ |
| description | The purpose of the present paper was to assess the ability of five newly designed and synthesized meloxicam analogues to interact with phospholipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of the chemical structure, the studied compounds penetrated bilayers and affected mainly their polar/apolar regions, closer to the surface of the model membrane. The influence of meloxicam analogues on the thermotropic properties of DPPC bilayers was clearly visible because these compounds reduced the temperature and cooperativity of the main phospholipid phase transition. Additionally, the studied compounds quenched the fluorescence of prodan to a higher extent than laurdan, what pointed to a more pronounced interaction with membrane segments close to its surface. We presume that a more pronounced intercalation of the studied compounds into the phospholipid bilayer may be related to the presence of the molecule of a two-carbon aliphatic linker with a carbonyl group and fluorine substituent/trifluoromethyl group (compounds <b>PR25</b> and <b>PR49</b>) or the three-carbon linker together with the trifluoromethyl group (<b>PR50</b>). Moreover, computational investigations of the ADMET properties have shown that the new meloxicam analogues are characterized by beneficial expected physicochemical parameters, so we may presume that they will have a good bioavailability after an oral administration. |
| first_indexed | 2024-03-11T04:45:40Z |
| format | Article |
| id | doaj.art-6bb28e01df17413bb941e599802de13b |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-11T04:45:40Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-6bb28e01df17413bb941e599802de13b2023-11-17T20:23:18ZengMDPI AGMembranes2077-03752023-04-0113441610.3390/membranes13040416New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence SpectroscopyJadwiga Maniewska0Justyna Gąsiorowska1Żaneta Czyżnikowska2Krystyna Michalak3Berenika M. Szczęśniak-Sięga4Department of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, T. Chałubińskiego 3a, 50-368 Wrocław, PolandDepartment of Basic Chemical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, PolandDepartment of Biophysics and Neuroscience, Wroclaw Medical University, T. Chałubińskiego 3a, 50-368 Wrocław, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, PolandThe purpose of the present paper was to assess the ability of five newly designed and synthesized meloxicam analogues to interact with phospholipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of the chemical structure, the studied compounds penetrated bilayers and affected mainly their polar/apolar regions, closer to the surface of the model membrane. The influence of meloxicam analogues on the thermotropic properties of DPPC bilayers was clearly visible because these compounds reduced the temperature and cooperativity of the main phospholipid phase transition. Additionally, the studied compounds quenched the fluorescence of prodan to a higher extent than laurdan, what pointed to a more pronounced interaction with membrane segments close to its surface. We presume that a more pronounced intercalation of the studied compounds into the phospholipid bilayer may be related to the presence of the molecule of a two-carbon aliphatic linker with a carbonyl group and fluorine substituent/trifluoromethyl group (compounds <b>PR25</b> and <b>PR49</b>) or the three-carbon linker together with the trifluoromethyl group (<b>PR50</b>). Moreover, computational investigations of the ADMET properties have shown that the new meloxicam analogues are characterized by beneficial expected physicochemical parameters, so we may presume that they will have a good bioavailability after an oral administration.https://www.mdpi.com/2077-0375/13/4/416model membranesDPPCDSCfluorescence spectroscopylaurdanprodan |
| spellingShingle | Jadwiga Maniewska Justyna Gąsiorowska Żaneta Czyżnikowska Krystyna Michalak Berenika M. Szczęśniak-Sięga New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy Membranes model membranes DPPC DSC fluorescence spectroscopy laurdan prodan |
| title | New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy |
| title_full | New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy |
| title_fullStr | New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy |
| title_full_unstemmed | New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy |
| title_short | New Meloxicam Derivatives—Synthesis and Interaction with Phospholipid Bilayers Measured by Differential Scanning Calorimetry and Fluorescence Spectroscopy |
| title_sort | new meloxicam derivatives synthesis and interaction with phospholipid bilayers measured by differential scanning calorimetry and fluorescence spectroscopy |
| topic | model membranes DPPC DSC fluorescence spectroscopy laurdan prodan |
| url | https://www.mdpi.com/2077-0375/13/4/416 |
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