ABSTRACT
A new series of 16E-arylidene androstene derivatives has been synthesized and evaluated for aromatase inhibitory activity. The impact of various aryl substituents at 16 position of the steroid skeleton on aromatase inhibitory activity has been observed. The 16E-arylidenosteroids 6, 10 and 11 exhibited significant inhibition of the aromatase enzyme. 16-(4-Pyridylmethylene)-4-androstene-3,17-dione (6, IC(50): 5.2 µM) and 16-(benzo-[1,3]dioxol-5-ylmethylene)androsta-1,4-diene-3,17-dione (11, IC(50): 6.4 µM) were found to be approximately five times more potent in comparison to aminoglutethimide.
Subject(s)
Aromatase Inhibitors/chemical synthesis , Aromatase/chemistry , Steroids/chemistry , Aminoglutethimide/chemistry , Aminoglutethimide/metabolism , Aminoglutethimide/pharmacology , Androstenes/chemistry , Aromatase/metabolism , Aromatase Inhibitors/chemistry , Protein Binding , Steroids/chemical synthesis , Steroids/metabolismABSTRACT
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.
