RESUMO
Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.
Assuntos
Antioxidantes/farmacologia , Antivirais/farmacologia , Polifenóis/farmacologia , Triazinas/farmacologia , Triazóis/farmacologia , Animais , Antioxidantes/síntese química , Antioxidantes/metabolismo , Antivirais/síntese química , Antivirais/metabolismo , Cães , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/efeitos dos fármacos , Células Madin Darby de Rim Canino , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Polifenóis/síntese química , Polifenóis/metabolismo , Ligação Proteica , Triazinas/síntese química , Triazinas/metabolismo , Triazóis/síntese química , Triazóis/metabolismoRESUMO
The efficacy of Triazavirin against the tick-borne encephalitis virus was estimated in the sensitive cell culture vs. the active drug Ribavirin. In a concentration of 128 mcg/ml Triazavirin was shown active in inhibition of the tick-borne encephalitis virus reproduction (strain Sofiin) by accumulation in the SKEV cell culture.
Assuntos
Antivirais/farmacologia , Azóis/farmacologia , Vírus da Encefalite Transmitidos por Carrapatos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Rim/efeitos dos fármacos , Triazinas/farmacologia , Animais , Antivirais/síntese química , Azóis/síntese química , Linhagem Celular , Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Células Epiteliais/citologia , Células Epiteliais/virologia , Rim/citologia , Rim/virologia , Ribavirina/farmacologia , Suínos , Triazinas/síntese química , Triazóis , Replicação Viral/efeitos dos fármacosRESUMO
The influence of 2-morpholino-5-(thienyl-2)-6-H-1,3,4-thiadiazine (H-29) on the platelet aggregation has been studied in experiments on donor plasma in vitro. It is established that H-29 causes a decrease in the platelet interaction induced by ADP and arachidonic acid. The influence of H-29 on platelet aggregation was also studied in ex vivo experiments with intravenous and oral administration, and some parameters of plasmatic hemostasis were evaluated.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Morfolinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Tiadiazinas/farmacologia , Difosfato de Adenosina/farmacologia , Animais , Ácido Araquidônico/farmacologia , Testes de Coagulação Sanguínea , Plaquetas/citologia , Humanos , Morfolinas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Contagem de Plaquetas , Coelhos , Tiadiazinas/síntese químicaRESUMO
A new class of inhibitors of herpes simplex virus replication was found. The compounds under study are derived from condensed 1,2,4-triazolo[5,1-c][1,2,4]triazines and 1,2,4-triazolo[1,5-a]pyrimidines, structural analogues of natural nucleic bases. Antiherpetic activity and cytotoxicity of the compounds were studied. The corresponding triphosphates of several active compounds were prepared and tested as inhibitors of DNA synthesis catalyzed by herpes simplex virus polymerase. The potential mechanism of their action is blocking of DNA dependent DNA polymerase, a key enzyme of viral replication.
Assuntos
Antivirais/química , Antivirais/farmacologia , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Triazinas/química , Triazinas/farmacologia , Triazóis/química , Triazóis/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular , Chlorocebus aethiops , DNA Polimerase Dirigida por DNA/metabolismo , Herpesvirus Humano 1/enzimologia , Humanos , Modelos Moleculares , Inibidores da Síntese de Ácido Nucleico , Polifosfatos/química , Polifosfatos/farmacologia , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
The influence of new original 1,3,4-thiadiazines on the human platelet aggregation in vitro was studied. All substances inhibited the platelet aggregation induced by both ADP and arachidonic acid. 1,3,4-Thiadiazines L-19, H-30 and L-37 were the most effective inhibitors. Effect of the intravenous injection of L-19 in various doses on platelet aggregation and some parameters of plasmatic hemostasis were studied ex vivo.
Assuntos
Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Tiadiazinas/farmacologia , Difosfato de Adenosina/farmacologia , Animais , Ácido Araquidônico/farmacologia , Avaliação Pré-Clínica de Medicamentos , Coelhos , Tiadiazinas/químicaRESUMO
A series of new 1,3,4-thiadiazine derivatives have been synthesized and their effect on the human platelet aggregation in vitro has been studied. All the tested substances inhibit the human platelet aggregation induced by ADP and arachidonic acid in a broad concentration range. The most active 1,3,4-thiadiazines (L-19, L-28 and L-31) effectively inhibit platelet aggregation at concentrations within 0.01-1 mM.