A study of myelostimulating activity of ionic compounds-trimecaine alkyl iodide derivatives under the cipher BIV (BIV-117, BIV-118, and BIV-119) was conducted on a model of doxorubicin pancytopenia in white laboratory rats. It was established that the compounds BIV-117 and BIV-119 had a pronounced leukopoiesis-stimulating activity, exceeding the activity of the methyluracil as a comparison drug. Compounds BIV-117 and BIV-119 had erythropoiesis- and thrombocytopoiesis-stimulating activity at the level of methyluracil.
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.
Spiroconnected N-alkoxyalkylpiperidine hydantoins were obtained via the Strecker reaction of cyanohydrin with ammonium carbonate. 1,3,8-Triazaspiro[4.5]decane-2,4-diones have shown the myelostimulating activity in the artificially induced (with cyclophosphamide) myelodepressive syndrome. The compounds significantly accelerated the regeneration of lymphocyte and granulocyte cell pool of bone marrow hematopoiesis.
1-(2-phenylethyl)-4-ketoxympiperidine o-fluorobenzoic acid hydrochloride, a complex with β-cyclodextrin p-fluorobenzene carbonylamide morpholine, a complex with β-cyclodextrin o-fluorobenzene carbonylamide piperidine had high myelostimulating activity at the level of the comparison drug methyluracil. 1-(3-ethoxypropyl)-4-ketoxympiperidine p-fluorobenzoic acid ester hydrochloride, 1-(2-phenylethyl)-4-ketoxympiperidine m-fluorobenzoic acid ester hydrochloride, 1-(2-phenylethyl)-4-ketoxympiperidine p-fluorobenzoic acid ester hydrochloride did not possess leukopoiesis-stimulating activity, but showed erythropoiesis-stimulating and thrombocytopoiesis-stimulating activity at the level of the comparison drug methyluracil.
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