Research Terms
Chemistry Chemical Reactions Chemical Synthesis
ACS, Member; 1983 - present
These new “curcuminoid-inspired” compounds show great promise as anti-cancer drugs. Through patent-pending synthetic methods, the resulting compounds exhibit substantially increased bioavailability and stability compared with unmodified curcuminoids. In-vitro bioassays of several of the compounds demonstrate remarkable antiproliferative and apoptotic effects against cancer cell lines at the nano-molar dosage.
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
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.
US Patent 10,934,241, and additional 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.
Opportunity
The University of North Florida is seeking companies interested in commercializing new synthetic methods for the preparation of pentauorosulfanyl (SF5) aromatic diazonium salts and the application of such salts as building blocks for a wide variety of compounds useful in biomedical, pharmaceutical, agricultural, and materials applications. The new methods developed at the University of North Florida facilitate access to a wide variety of SF5-aromatic compounds whose synthesis by other means is challenging and not economical due to their reliance on exotic/hazardous reagents and harsh conditions.
Application
SF5-bearing molecules have important biological properties and are of current interest in a wide variety of fields. The development of synthetic methods in this invention enable facile access to novel SF5-aromatics and to a large assortment of SF5-bearing molecules for use in high-performance polymers, liquid crystals, pharmaceuticals, and pesticides, areas that are highly dependent on the availability of these small molecule building blocks for producing functional compounds
Invention Details
Compounds in the pentauorosulfanyl (SF5) group impart a number of favorable physical and chemical characteristics including thermal, hydrolytic, and chemical stability, high density, high electronegativity, and high lipophilicity. These favorable characteristics have prompted a high degree of interest in SF5-organics for practical applications in the biomedical, agricultural, and materials elds. This invention provides a versatile, readily available, and easily produced starting pentauorosulfanyl-substituted compound for use in pentauorosulfanyl-based synthesis. Specically, the invention allows for the synthesis and isolation of 4-(pentauorosulfanyl)benzenediazonium tetrauoroborate salt, which can be further deployed in a wide assortment of reactions to form novel SF5-bearing alkenes, alkynes, and biaryl derivatives, demonstrating the broad utility of pentauorosulfanyl diazonium salts as building blocks of SF5-aromatics.
