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


Yu V. Balabekova M. Ten A. Zharkynbek T. Koks S. Alimova M. Koizhaiganova R. Mussilim M. Malmakova A. Seilkhanov T. Tassibekov K.
July 2025Multidisciplinary Digital Publishing Institute (MDPI)

Molecules
2025#30Issue 13

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.

acute pneumonia , complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with β-Cyclodextrin ((o-Fph)PPhβCD) , immunomodulation , Polyoxidonium (PO) , regulatory T cells

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Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Ualikhanov St., Almaty, 050010, Kazakhstan
Pathological Physiology Department, Asfendiyarov Kazakh National Medical University, 94 Tole-bi St., Almaty, 050000, Kazakhstan
Health Futures Institute, Murdoch University, 90 South St., Perth, 6150, WA, Australia
Laboratory of Engineering Profile NMR Spectroscopy, Sh. Ualikhanov Kokshetau State University, 76 Abai St., Kokshetau, 020000, Kazakhstan

Laboratory of Synthetic and Natural Medicinal Compounds Chemistry
Pathological Physiology Department
Health Futures Institute
Laboratory of Engineering Profile NMR Spectroscopy

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