RESUMO
A new series of N-substituted imide derivatives have been synthesized by treating phthalic anhydride, naphthalic anhydride and their substituted derivatives with 2-hydrazino-1-imidazoline hydrobromide, various para-substituted aryl amines, aminoglutethimide and 2,4-dinitrophenyl hydrazine. Compounds 9, 10, 12, 18, 19, 23, 24 and 34-36 have been selected and screened for antineoplastic activity by National Cancer Institute, Bethesda, USA. Some newer aminoglutethimide derivatives 37-39 have also been prepared in order to study the effect of N-substitution on its pharmacological profile for the treatment of carcinoma. These compounds (37-39) have exhibited weak inhibition of human placental aromatase as compared to aminoglutethimide.
Assuntos
Antineoplásicos/síntese química , Inibidores da Aromatase/síntese química , Imidas/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores da Aromatase/química , Inibidores da Aromatase/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imidas/química , Imidas/farmacologia , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
A novel dimer of 2-(4-pyridylmethyl)-1-indanone (2) was obtained while carrying out aldol condensation of 1-indanone with pyridine-4-carboxaldehyde in potassium hydroxide. The structure of dimer 3 has been established using various spectral techniques and was screened for its ability to inhibit the cytochrome P(450) enzyme aromatase. The dimer showed strong inhibition of human placental aromatase and was found 3 times more potent (RP = 3, IC(50) = 10.2 microM) as compared to aminoglutethimide (RP = 1, IC(50) = 18.5 microM.
