Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation
Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4<sup>+</sup>, CD4<sup>+</sup>CD25<sup>+</sup>, and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>, which are cr...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/13/2741 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849319892373733376 |
|---|---|
| author | Valentina Yu Marina Balabekova Assel Ten Tolganay Zharkynbek Sulev Koks Milana Alimova Raushan Koizhaiganova Meruyert Mussilim Aigul Malmakova Tulegen Seilkhanov Khaidar Tassibekov |
| author_facet | Valentina Yu Marina Balabekova Assel Ten Tolganay Zharkynbek Sulev Koks Milana Alimova Raushan Koizhaiganova Meruyert Mussilim Aigul Malmakova Tulegen Seilkhanov Khaidar Tassibekov |
| author_sort | Valentina Yu |
| collection | DOAJ |
| description | Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4<sup>+</sup>, CD4<sup>+</sup>CD25<sup>+</sup>, and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> significantly restored CD4<sup>+</sup> and CD4<sup>+</sup>CD25<sup>+</sup> T-cell levels and induced a sustained reduction in regulatory CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> exerted a more prolonged response, which was particularly evident by day 14. Structural confirmation of the inclusion complex was achieved through IR and NMR spectroscopy. These findings highlight (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation. |
| format | Article |
| id | doaj-art-c845e13e645e4aba915b48f36aff0ce2 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-c845e13e645e4aba915b48f36aff0ce22025-08-20T03:50:17ZengMDPI AGMolecules1420-30492025-06-013013274110.3390/molecules30132741Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary InflammationValentina Yu0Marina Balabekova1Assel Ten2Tolganay Zharkynbek3Sulev Koks4Milana Alimova5Raushan Koizhaiganova6Meruyert Mussilim7Aigul Malmakova8Tulegen Seilkhanov9Khaidar Tassibekov10Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, KazakhstanPathological Physiology Department, Asfendiyarov Kazakh National Medical University, 94 Tole-bi St., Almaty 050000, KazakhstanLaboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, KazakhstanLaboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, KazakhstanHealth Futures Institute, Murdoch University, 90 South St., Perth, WA 6150, AustraliaPathological Physiology Department, Asfendiyarov Kazakh National Medical University, 94 Tole-bi St., Almaty 050000, KazakhstanLaboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, KazakhstanPathological Physiology Department, Asfendiyarov Kazakh National Medical University, 94 Tole-bi St., Almaty 050000, KazakhstanLaboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, KazakhstanLaboratory of Engineering Profile NMR Spectroscopy, Sh. Ualikhanov Kokshetau State University, 76 Abai St., Kokshetau 020000, KazakhstanLaboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, KazakhstanAcute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4<sup>+</sup>, CD4<sup>+</sup>CD25<sup>+</sup>, and CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> significantly restored CD4<sup>+</sup> and CD4<sup>+</sup>CD25<sup>+</sup> T-cell levels and induced a sustained reduction in regulatory CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> exerted a more prolonged response, which was particularly evident by day 14. Structural confirmation of the inclusion complex was achieved through IR and NMR spectroscopy. These findings highlight (<b><i>o</i>-Fph</b>)<b>PPhβCD</b> as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation.https://www.mdpi.com/1420-3049/30/13/2741complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>)Polyoxidonium (PO)acute pneumoniaregulatory T cellsimmunomodulation |
| spellingShingle | Valentina Yu Marina Balabekova Assel Ten Tolganay Zharkynbek Sulev Koks Milana Alimova Raushan Koizhaiganova Meruyert Mussilim Aigul Malmakova Tulegen Seilkhanov Khaidar Tassibekov Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation Molecules complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>) Polyoxidonium (PO) acute pneumonia regulatory T cells immunomodulation |
| title | Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation |
| title_full | Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation |
| title_fullStr | Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation |
| title_full_unstemmed | Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation |
| title_short | Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation |
| title_sort | targeted restoration of t cell subsets by a fluorinated piperazine derivative β cyclodextrin complex in experimental pulmonary inflammation |
| topic | complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((<b><i>o</i>-Fph</b>)<b>PPhβCD</b>) Polyoxidonium (PO) acute pneumonia regulatory T cells immunomodulation |
| url | https://www.mdpi.com/1420-3049/30/13/2741 |
| work_keys_str_mv | AT valentinayu targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT marinabalabekova targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT asselten targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT tolganayzharkynbek targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT sulevkoks targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT milanaalimova targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT raushankoizhaiganova targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT meruyertmussilim targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT aigulmalmakova targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT tulegenseilkhanov targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation AT khaidartassibekov targetedrestorationoftcellsubsetsbyafluorinatedpiperazinederivativebcyclodextrincomplexinexperimentalpulmonaryinflammation |