RESUMO
New water-soluble antiviral chemical agents, containing 10 to 30% of adamantane derivatives (amino-, aminopropyl-adamantane-, aminomethyl- and rimantadine), which were conjugated with polycarboxylic matrixes of the divinyl ether and maleic anhydride copolymers (DIVEMA), were developed. The polymeric drugs exhibited a low cytotoxicity (4 to 10 times less than rimantadine) and a wide spectrum of antiviral activity against influenza viruses, including both the remantadine-resistant strains of A/PR/8/34 (H1N1) and the B/Saint-Petersburg strain/71/77 as well as against herpes viruses of type 1, parainfluenza viruses of types 1 and 3 and RS-virus. A reduction of the viral infection titer in their reproduction in sensitive cells' cultures was more than 2.0 Ig ID50. Complete inhibition of viral-specific syntheses, registered by immune-enzyme assay (IEA) and by hemagglutination test was observed at low infection doses ranging from 1 to 100 ID50. The efficiency of the antiviral effect depends on a drug's molecular weight and a structure of chemical bonds between the adamantane nucleus and the polymeric matrix.
Assuntos
Adamantano/análogos & derivados , Antivirais/farmacologia , Polímeros/farmacologia , Animais , Linhagem Celular , Efeito Citopatogênico Viral/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Farmacorresistência Viral , Herpesviridae/efeitos dos fármacos , Humanos , Peso Molecular , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/imunologia , Polímeros/síntese química , Copolímero de Pirano/síntese química , Copolímero de Pirano/farmacologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Respirovirus/efeitos dos fármacos , Respirovirus/imunologia , Rimantadina/farmacologia , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
A series of lipophilic derivatives of the copolymer divinyl ether with maleic anhydride were synthesized and tested for their effects on immunocompetent cells. Increases in the length of a hydrophobic moiety and its quantity in the polymer chain of the agent were demonstrated to substantially modify the factors of animals' humoral and cell-mediated immunity. This phenomena is well associated with the examined superficial qualities of solutions of the agents and their mycelium forming capacity.
Assuntos
Linfócitos B/efeitos dos fármacos , Anidridos Maleicos/farmacologia , Linfócitos T/efeitos dos fármacos , Compostos de Vinila/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Linfócitos B/imunologia , Imunidade Celular/efeitos dos fármacos , Anidridos Maleicos/química , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Polímeros , Linfócitos T/imunologia , Compostos de Vinila/químicaRESUMO
The virus-inhibiting and immunostimulating activity of Soviet preparations, maleic anhydride copolymers, was demonstrated in alpha-, flavi-, and bunyavirus infections. Positive results were obtained in subcutaneous and intraperitoneal inoculations of the preparations used in prophylactic and therapeutic-prophylactic schedules. Stimulation of vaccination immunity was observed after combined use of copolymers and the vaccine against Eastern equine encephalomyelitis.