Isoflavone derivatives as affinity tags for drug targeting Inventors

Dr. Dalia Somian, Institute Endocrinology, Metabolism and Hypertension, Tel Aviv Medical Center

Dr. Fortune Kohen, The Weizmann Institute of Science
Isoflavones,are plant derived molecules having specific affinity for estrogen receptors., Researches at TASMC together with WIS found that isoflavones are altered into chemotherapy carriers that serve as "homing devices" to ensure low-dose, cell-specific drug therapy. This property was demonstrated in various animal cancer modelsand  may also be used to carry contrast material to cancer cells as part of disease surveillance.

Technology's Essence

The present invention relates to the synthesis and evaluation of novel carboxy derivatives of isoflavones as selective estrogen receptor modulators (SERMs) and as carriers for targeting of cytotoxic drugs to normal or malignant cells expressing ERbeta. These carboxy derivatives of isoflavones displayed estrogenic properties in vitro in stimulating DNA synthesis in normal and malignant cells expressing ER b.

When tested in vivo, unlike the parent isoflavone, the carboxy derivatives of isoflavones showed antagonist like activity, at concentrations lower than the SERM raloxifene, in blocking in rat tissues the stimulatory response to estrogen on creatine kinase specific activity. These carboxy derivatives were subsequently conjugated to the cytotoxic drug daunomycin to yield cytotoxic isoflavone conjugates. When the cytotoxicity of these conjugates were evaluated in normal and malignant cells expressing ER b, the cytotoxicity of these conjugates were receptor mediated and caused inhibition of cell proliferation at concentrations much lower than daunomycin.