Design, Characterization, and Hematopoietic Efficacy of a Fluorinated Pyrazolopiperidine Inclusion Complex
Koshetova Z. Daulet G. Ten A. Koizhaiganova R. Baktybayeva L. Zharkynbek T. Zazybin A. Seilkhanov T. Zhumanova N. Dembitsky V. Yu V.
October 2025Multidisciplinary Digital Publishing Institute (MDPI)
Molecules
2025#30Issue 20
A novel inclusion complex of a fluorinated pyrazolopiperidine derivative (5-benzyl-7-(2-fluorobenzylidene)-2,3-bis(2-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine hydrochloride, PP·HCl) with β-cyclodextrin (PPβCD) was designed, synthesized, and characterized as a potential therapeutic agent for chemotherapy-induced myelosuppression and lymphopenia. Encapsulation of PP within β-cyclodextrin increased aqueous solubility by approximately 3.4-fold and improved dissolution rate by 2.8-fold compared with the free compound. Structural analysis using IR, ^1H/^13C NMR, and TLC confirmed the formation of a stable 1:1 host–guest complex, and the disappearance of free PP signals further supported complete encapsulation. In vivo evaluation in a cyclophosphamide-induced myelosuppression model demonstrated that PPβCD accelerated hematopoietic recovery, restoring leukocyte and erythrocyte counts 35–40% faster than methyluracil, without any signs of systemic toxicity. These findings indicate that β-cyclodextrin complexation significantly enhances solubility, dissolution, and biological efficacy of the pyrazolopiperidine scaffold, supporting further preclinical development of PPβCD as a supportive therapy for chemotherapy-related hematological complications.
complex β-Cyclodextrin with 5-benzyl-7-(2-fluorobenzylidene)-2,3-bis(2-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine (PPβCD) , cyclophosphamide , lymphocytopoietic-stimulating activity , myelopoietic-stimulating activity
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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
Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, 71 Al-Farabi Ave., Almaty, 050040, Kazakhstan
School of Chemical Engineering, Kazakh-British Technical University, 59 Tole Bi St., Almaty, 050000, Kazakhstan
Laboratory of Engineering Profile NMR Spectroscopy, Sh. Ualikhanov Kokshetau State University, 76 Abai St., Kokshetau, 020000, Kazakhstan
Department of Chemistry, Kazakh National Women’s Teacher Training University, 114 K1 Gogol St., Almaty, 050000, Kazakhstan
Centre for Applied Research, Innovation and Entrepreneurship, Lethbridge Polytechnic, 3000 College Drive South, Lethbridge, T1K 1L6, AB, Canada
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry
Department of Biophysics
School of Chemical Engineering
Laboratory of Engineering Profile NMR Spectroscopy
Department of Chemistry
Centre for Applied Research
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