Yu Valentina, Balabekova Marina, Ten Assel, Zharkynbek Tolganay, Koks Sulev, Alimova Milana, Koizhaiganova Raushan, Mussilim Meruyert, Malmakova Aigul, Seilkhanov Tulegen, Tassibekov Khaidar
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.
Molecules. 2025 Jun 25;30(13):2741. doi: 10.3390/molecules30132741.
Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4, CD4CD25, and CD4CD25FoxP3, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin (()), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that () significantly restored CD4 and CD4CD25 T-cell levels and induced a sustained reduction in regulatory CD4CD25FoxP3 cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, () 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 () as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation.
急性肺炎常伴有免疫抑制，尤其影响T细胞亚群，如对免疫调节至关重要的CD4、CD4CD25和CD4CD25FoxP3。本研究在油酸诱导的大鼠急性肺炎模型中，评估了一种与β-环糊精络合的新型氟化哌嗪基氨基膦酸酯（()）的免疫调节潜力，并将其与临床批准药物聚氧化乙烯（PO）进行比较。流式细胞术分析显示，()显著恢复了CD4和CD4CD25 T细胞水平，并使调节性CD4CD25FoxP3细胞持续减少，提示效应器免疫活性增强。虽然PO提供了早期免疫恢复作用，但()的反应更为持久，在第14天时尤为明显。通过红外光谱和核磁共振光谱对包合物进行了结构确认。这些发现突出了()作为一种有前景的免疫治疗候选物，能够在急性肺部炎症期间重新平衡免疫细胞群体并支持宿主防御机制。
