RESUMO
CONTEXT: Inhibition of pathological angiogenesis. OBJECTIVE: Obtaining new transactivator, bifunctional, thyroid antagonist, non-toxic anti-angiogenic compounds. MATERIALS AND METHODS: In silico drug design, synthesis in bulk and biological evaluation in chick chorioallantoic membrane (CAM) model. RESULTS: Significant inhibition (range 65-73%) at 0.25-2.0 µg/ml doses. DISCUSSION AND CONCLUSION: The synthesis of compounds (9), (10), and (11) incorporating long-chain moieties guanidine, urea, methyl amine and, propyl amine substitutions, respectively, into the core molecular framework of tetrac (tetraiodothyroacetic acid) were undertaken. The evaluation of the anti-angiogenic bioactivity of these compounds in the CAM model revealed no loss of activity in comparison with tetrac and XT199, which showed nearly 86% inhibition at dose levels of 1 and 0.5 µg/ml, respectively, and validated the concept.
Assuntos
Inibidores da Angiogênese/farmacologia , Desenho de Fármacos , Integrina alfaVbeta3/antagonistas & inibidores , Glândula Tireoide/efeitos dos fármacos , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Animais , Galinhas , Relação Dose-Resposta a Droga , Ovos , Modelos Moleculares , Estrutura MolecularRESUMO
Research on dual inhibitors of both 5-LOX and COXs gained interest due to the overexpressions of these enzymes during the malignant state of the evolution of prostate cancer. In order to take part in this research, new N-aroyl-tetrahydro-gamma-carbolines issued from the modification of Indomethacin have been synthesised. As for the NSAIDs, the compounds have been tested for their activity against COX(1), COX(2) plus against 5-LOX and against the proliferation of malignant prostate cancer. Interesting cytotoxic activities and selectivities of some tetrahydro-gamma-carboline derivatives have been obtained.
Assuntos
Carbolinas/síntese química , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Lipoxigenase , Neoplasias da Próstata/tratamento farmacológico , Anti-Inflamatórios não Esteroides/farmacologia , Carbolinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Humanos , Indometacina , Masculino , Relação Estrutura-AtividadeRESUMO
Novel thyroxine analogs with hindered phenol, amino and carboxylic acid groups have been synthesized and the effects of the synthesized compounds on angiogenesis using the chick chorioallantoic membrane and mouse matrigel models have been tested. Pharmacological profiles revealed that thyroxine tolerates numerous modifications on the amino group and remains active. These results provide the rationale for the selection of a novel thyroxine nanoparticle precursor.
Assuntos
Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/farmacologia , Tiroxina/síntese química , Tiroxina/farmacologia , Animais , Embrião de Galinha , Camundongos , Modelos Moleculares , Tiroxina/análogos & derivadosRESUMO
Novel Tetrac analogs were synthesized and then tested. Anti-angiogenesis efficacy was carried out using the Chick Chorioallantoic Membrane (CAM) model and the mouse matrigel model for angiogenesis. Pharmacological activities showed Tetrac can accommodate numerous modifications and maintain anti-angiogenesis activity.