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

Valentina Yu; Marina Balabekova; Assel Ten; Tolganay Zharkynbek; Sulev Koks; Milana Alimova; Raushan Koizhaiganova; Meruyert Mussilim; Aigul Malmakova; Tulegen Seilkhanov; Khaidar Tassibekov

doi:10.3390/molecules30132741

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

Journal article

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

Valentina Yu, Marina Balabekova, Assel Ten, Tolganay Zharkynbek, Sulev Koks, Milana Alimova, Raushan Koizhaiganova, Meruyert Mussilim, Aigul Malmakova, Tulegen Seilkhanov, …

Molecules (Basel, Switzerland), Vol.30(13), 2741

2025

DOI: https://doi.org/10.3390/molecules30132741

PMID: 40649259

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Abstract

complex of dimethyl[(4-benzhydrylpiperazin-1-yl)(2-fluorophenyl)methyl]phosphonate with beta-Cyclodextrin ((<bold><italic>o</italic>-Fph</bold>)<bold>PPh beta CD</bold>)

Polyoxidonium (PO)

acute pneumonia

regulatory T cells

immunomodulation

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.

Details

Title: Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation
Authors/Creators: Valentina Yu
Marina Balabekova
Assel Ten
Tolganay Zharkynbek
Sulev Koks - Murdoch University, Personalised Medicine Centre
Milana Alimova - Kazakh National Medical University
Raushan Koizhaiganova
Meruyert Mussilim - Kazakh National Medical University
Aigul Malmakova
Tulegen Seilkhanov
Khaidar Tassibekov
Publication Details: Molecules (Basel, Switzerland), Vol.30(13), 2741
Publisher: MDPI
Number of pages: 17
Grant note: AP19675500 / Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan 483 / Asfendiyarov Kazakh National Medical University, under the project titled: “Prognostic Role of the Tumor Microenvironment in Targeted Modulation of Immune System Components During Acute Pneumonia and the Development of Novel Pathogenetic Correction Strategies”
Identifiers: 991005794762407891
Murdoch Affiliation: Health Futures Institute; Personalised Medicine Centre; Genomics Core Research Facility
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.26 Diabetes; 1.26.1850 Hospital Glycemic Control
Web Of Science research areas: Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
ESI research areas: Chemistry