metapristone and Breast-Neoplasms

Novel gadolinium-based mifepristone conjugates were synthesised using various synthetic routes. Moderate antiprogestagenic activity of the new conjugates was observed in human breast cancer cells (T47-D cells) using AP (alkaline phosphatase) assay. The amount of incorporated Gd determined by inductively coupled plasma mass spectroscopy (ICPMS) indicates the number of binding sites per cell. These conjugates might be important compounds to develop receptor-targeted MRI contrast agents as well as other anti-breast cancer therapeutics.

Topics: Binding Sites; Breast Neoplasms; Cell Line, Tumor; Coordination Complexes; Female; Gadolinium; Humans; Magnetic Resonance Imaging; Mifepristone; Receptors, Progesterone

A series of mifepristone derivatives with different "linker groups" in position 4' of the phenyl ring in the 11beta-position of the steroid scaffold (2-41) have been synthesized. Their antigestagenic activites were determined in a cell-based assay (alkali phosphatase assay in T47-D breast cancer cells) and compared with that of the parent compound mifepristone. SAR and QSAR studies reveal the influence of both lipophilicity and partial charge based van der Waals surface area descriptors on biological activity. Within the series of compounds described in this study, three mifepristone derivatives are identified with considerably high antigestagenic activity. These compounds are regarded as useful starting materials for the synthesis of either physiologically stable or cleavable progesterone receptor-binding conjugates for therapeutic or diagnostic purposes.

Topics: Alkaline Phosphatase; Breast Neoplasms; Cell Line, Tumor; Female; Hormone Antagonists; Humans; Mifepristone; Models, Molecular; Neoplasms, Hormone-Dependent; Receptors, Progesterone; Regression Analysis; Structure-Activity Relationship