Download Isoflavone derivatives as affinity tags for drug targeting

Isoflavone derivatives as affinity tags for drug targeting
Inventors
Prof. Naftalie Stern, Director, Institute Endocrinology, Metabolism and
Hypertension, Tel Aviv Medical Center
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.
Applications
Therapy:
(i)
carboxy
derivatives
of
isoflavones
may
serve
as
SERMs
(ii) the cytotoxic isoflavones, prepared from the carboxy derivatives of the
isoflavones, may be used for affinity drug targeting of tumors carrying ER b in vivo.
Diagnosis and Imaging: These carboxy derivatives of isoflavones are amenable for
conjugation to other markers [e.g. DTPA conjugated to paramagnetic particles (e.g.
gadolinium) or radioactive Indium] for magnetic resonance imaging or other imaging
technologies for ER b positive tissues.