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Molecules
Volume 30
Issue 13
10.3390/molecules30132741
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation

by
Valentina Yu
1,
Marina Balabekova
2,*,
Assel Ten
1,
Tolganay Zharkynbek
1,*,
Sulev Koks
3,
Milana Alimova
2,
Raushan Koizhaiganova
1,
Meruyert Mussilim
2,
Aigul Malmakova
1,
Tulegen Seilkhanov
4 and
Khaidar Tassibekov
1
1
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan
2
Pathological Physiology Department, Asfendiyarov Kazakh National Medical University, 94 Tole-bi St., Almaty 050000, Kazakhstan
3
Health Futures Institute, Murdoch University, 90 South St., Perth, WA 6150, Australia
4
Laboratory of Engineering Profile NMR Spectroscopy, Sh. Ualikhanov Kokshetau State University, 76 Abai St., Kokshetau 020000, Kazakhstan
*
Authors to whom correspondence should be addressed.
Molecules 2025, 30(13), 2741; https://doi.org/10.3390/molecules30132741 (registering DOI)
Submission received: 30 May 2025 / Revised: 20 June 2025 / Accepted: 23 June 2025 / Published: 25 June 2025
(This article belongs to the Special Issue Heterocycles: Design, Synthesis and Biological Evaluation, 3rd Edition)
Versions Notes

Abstract

Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4+, CD4+CD25+, and CD4+CD25+FoxP3+, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((o-Fph)PPhβCD), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (o-Fph)PPhβCD significantly restored CD4+ and CD4+CD25+ T-cell levels and induced a sustained reduction in regulatory CD4+CD25+FoxP3+ cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (o-Fph)PPhβCD 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 (o-Fph)PPhβCD as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation.
Keywords: complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((o-Fph)PPhβCD); Polyoxidonium (PO); acute pneumonia; regulatory T cells; immunomodulation complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((o-Fph)PPhβCD); Polyoxidonium (PO); acute pneumonia; regulatory T cells; immunomodulation

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MDPI and ACS Style

Yu, V.; Balabekova, M.; Ten, A.; Zharkynbek, T.; Koks, S.; Alimova, M.; Koizhaiganova, R.; Mussilim, M.; Malmakova, A.; Seilkhanov, T.; et al. Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation. Molecules 2025, 30, 2741. https://doi.org/10.3390/molecules30132741

AMA Style

Yu V, Balabekova M, Ten A, Zharkynbek T, Koks S, Alimova M, Koizhaiganova R, Mussilim M, Malmakova A, Seilkhanov T, et al. Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation. Molecules. 2025; 30(13):2741. https://doi.org/10.3390/molecules30132741

Chicago/Turabian Style

Yu, Valentina, Marina Balabekova, Assel Ten, Tolganay Zharkynbek, Sulev Koks, Milana Alimova, Raushan Koizhaiganova, Meruyert Mussilim, Aigul Malmakova, Tulegen Seilkhanov, and et al. 2025. "Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation" Molecules 30, no. 13: 2741. https://doi.org/10.3390/molecules30132741

APA Style

Yu, V., Balabekova, M., Ten, A., Zharkynbek, T., Koks, S., Alimova, M., Koizhaiganova, R., Mussilim, M., Malmakova, A., Seilkhanov, T., & Tassibekov, K. (2025). Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation. Molecules, 30(13), 2741. https://doi.org/10.3390/molecules30132741

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