Improvement of myelopoiesis in a cyclophosphamide-induced myelodepression model by administration of a Newly Synthesized Pyrazolo- Piperidine β-Cyclodextrine complex compound

Abstract

According to WHO, the acquired secondary form of hematopoietic-depressive states increases the risk of death in people with cancer, infectious, and hormonal diseases. The choice of drugs that stimulate the proliferative activity of bone marrow cells is limited. The stimulus to the search for hematopoietic-stimulating compounds among pyridine derivatives was the manifestation of the activity of the cerebroprotective drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) to restore the granulocytes and B-lymphocytes homeostasis in clinical practice. The hematopoietic-stimulating activity of the newly synthesized compound Complex of 5-benzyl-7-(o-fluorobenzylidene)-2,3-bis(o-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine complex with β-cyclodextrin (BIV) was studied on a model of cyclophosphamide-induced myelodepression in C57BL6/J mouse line. The BIV compound demonstrated a stimulating effect on the process of restoring the level of Ly-6G+ Ly-6C+ granulocytes, monocytes/macrophages, CD19+ B-lymphocytes in the bone marrow, exceeding the activity of the reference drug Methyluracil. The BIV compound did not affect on the proliferative activity of c-kit (CD117+)-expressing cells, CD3e+ pre-T-lymphocytic cells and Ter-119+ erythroid cells in the bone marrow. The total number of bone marrow myelokaryocytes in the experimental groups was significantly higher than in the intact group. The pronounced hematopoietic-stimulating effect of the BIV compound gives in the future the prospect of development as a drug used for the treatment of B-lymphocytic and granulocytic-macrophage hematopoietic-depressive states.

Stimulation of B-Lymphopoiesis by Administration of a Trimecaine-Based Ionic Compound in Cyclophosphamide-Induced Hematopoietic-Depressive Model

“…JNM-ECA “Jeol 400” spectrometer (Jeol, Tokio, Japan) was used to record 1 H (working frequency 399.78 MHz) and 13 C (working frequency 100.53 MHz) NMR spectra with CDCl 3 solvent. The residual protons (7.26 ppm) and carbon atom (77.0 ppm) signals of CDCl 3 were used to determine chemical shifts [ 43 ]. The melting point is a criterion for the purity of a substance.…”

“…Contaminating erythrocytes were lysed with lysing solution (0.83% NH 4 Cl, 0.1% KHCO 3 , 0.003% EDTA, pH 7.2–7.4) for 10 min at room temperature, then cells were washed, filtered through 30 mL preparation filters (Miltenyi Biotec, San Jose, CA, USA), and re-suspended in PBS. Cells were counted and their viability was determined using trypan blue [ 43 ].…”