RESUMO
Granulocytic CSF pegylated using electron-beam synthesis nanotechnology exhibits pronounced granulomonocytopoiesis-stimulating and SC-mobilizing activity. More potent stimulation of committed precursors against the background of less pronounced activation of polypotent hemopoietic cells is a peculiarity of hemostimulating action of pegylated using electron-beam synthesis nanotechnology granulocytic CSF in comparison with its non-modified analog. The mobilizing effect of pegylated using electron-beam synthesis nanotechnology granulocytic CSF on early progenitor elements surpasses that of non-conjugated cytokine.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Hematínicos/farmacologia , Polietilenoglicóis/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Contagem de Células , Ciclofosfamida/farmacologia , Fator Estimulador de Colônias de Granulócitos/síntese química , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Hematínicos/síntese química , Hematopoese/efeitos dos fármacos , Humanos , Imunossupressores/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos CBA , Nanotecnologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Distribuição de Poisson , Polietilenoglicóis/síntese química , Estatísticas não ParamétricasAssuntos
Complexo Ferro-Dextran/efeitos adversos , Animais , Testes de Carcinogenicidade , Carcinógenos/síntese química , Carcinógenos/química , Carcinógenos/farmacologia , Carcinógenos/toxicidade , Cricetinae , Feminino , Regulamentação Governamental , Guias como Assunto , Hematínicos/efeitos adversos , Hematínicos/síntese química , Hematínicos/química , Hematínicos/toxicidade , Humanos , Complexo Ferro-Dextran/síntese química , Complexo Ferro-Dextran/química , Complexo Ferro-Dextran/toxicidade , Masculino , Camundongos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/legislação & jurisprudência , Coelhos , Ratos , Estados UnidosRESUMO
A series of TAN-1511 analogues bearing a non-peptide spacer in place of the Gly-Gly-Gly sequence in the peptide moiety was synthesized, and the effects of these compounds on the proliferation of bone marrow cells in culture and experimental leukocytopenia in mice were examined. The structure-activity relationships obtained were as follows. As the substituent at the 2-position of the 4-thiaheptanoic acid framework, an amino group, methyl group or hydrogen was preferable; as a spacer in place of the Gly-Gly-Gly sequence, a 4-aminobenzoyl or 4-aminomethylbenzoyl group was suitable; and as the fatty acids bonded to the 6,7-dihydroxy groups, C16 fatty acid was best. Compounds 12f, 30d and 30i potently promoted the proliferation of bone marrow cells in culture and the restoration of leukocyte counts in a murine leukocytopenia model.
