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Anti-Cancer Synthetic Curcuminoids

Opportunity

The University of North Florida is seeking companies interested in commercializing “curcuminoidinspired” synthetic compounds that show great promise as anticancer drugs. The compounds are prepared by modular and efficient synthetic methods that introduce diverse activating/deactivating polar substituents including the SCF3, OCF3, and F groups to increase lipophilicity, bioavailability, and metabolic stability. These flexible methods also enable synthesis of heterocyclic curcuminoids.
Advantages
Provides anti-proliferative and apoptotic effects against cancer cell
lines at nano-molar doses.

Bioassay results show comparatively little impact on healthy cells.

Improved metabolic stability and physiochemical properties by introduction of fluorinated moieties such as SCF3, OCF3, and F groups.

Application

Several synthesized compounds have been tested by in-vitro bioassay at the National Cancer Institute through the Developmental Therapeutics Program, as well as at the Mayo Clinic Jacksonville by cell viability assay to determine EC50 using a myeloma cell line versus cells from healthy donors. Several “hit” compounds have been identified that exhibit remarkable antiproliferative and apoptotic effects at the nano-molar dosage. These compounds are especially effective against leukemia and myeloma—with a 500-fold difference in EC50 values in the Mayo study suggesting highly tumor-specific activity—but also show strong responses to other cancer cell lines.

Invention Details

Curcumin (CUR) has a combination of features that provide it with a unique ability to interact with target proteins. However, a major obstacle toward the development of curcumin-derived cancer drugs is low bioavailability due to rapid metabolism as well as poor water solubility and lipophilicity. To overcome this, practical and high-yielding methods have been developed for the synthesis of CUR-BF2 adducts and CURs bearing trifluoromethylthio (CF3S), trifluoromethoxy (CF3O), trifluoromethyl (CF3) groups as well as fluorines. Methods have also been invented for selective fluorine introduction into the alpha-carbonyl region. These studies improve physiochemical properties of these curcuminoids. Additional derivatizations included synthesis of a host of pyrazoles and oxazoles. Methods have also been developed for the synthesis of a host of heterocyclic CUR compounds and their BF2-adducts. The resulting synthetic compounds have been isolated, characterized, and successfully tested against multiple cancer cell lines. Computational docking studies also have been performed to compare binding efficiency to target proteins involved in specific cancers versus known inhibitor drugs. For several compounds, the computed binding energies are comparable to or better than known anticancer drugs.

 

Patent Pending. Invented by Dr. Kenneth Laali, Department of Chemistry. Relevant publications include Journal of Fluorine Chemistry 2016, 191, 29–41. 

More Information: John Kantner, Associate VP for Research, j.kantner@unf.edu, (904) 620-2455.