Anticancer Agents and Antibiotic Polymers (2011 - Present)

Investigator:  John Williams, Rhode Island College

Abstract:  Tamoxifen and GSK-4716 mimics have been synthesized in our labs. We have identified compounds with estrogenic or anti-estrogenic activity or both, with no off-target toxicity, in multi-plate screenings against the estrogen receptor alpha in each subclass of mimic structures; triarylethenes, triaryltriazoles, diarylimines and triarylimines and arylphosphonium salts.  Active molecules in all groups have shown binding constants of the same order as tamoxifen in computer screening studies using the eHitsLightening® docking software. We have added microwave acceleration to the synthesis methods and HPLC to isolation and analysis. The current project will exploit this work and extend it to synthesis of new estrogen-active compounds and have them screened in collaboration with research faculty at the U of Fla. W.H. Anderson Cancer Center, USCLA School of Pharmacy, and the Kansas State U School of Veterinary Medicine.

Antibiotic polymers are potentially useful in fabricating medical plastics. Interiors of bags and tubes provide surfaces where resistant strains of bacteria can colonize and form biofilms. Covalently-bound antibiotics can suppress them.  We have done proof of principle experiments using microwave accelerated synthesis as well as traditional bench top methods on graft polymers to cotton and polyvinyl alcohol that show antibiotic activity. Some of these are being characterized by thermal gravimetry and differential thermal calorimetry using the instrumentation at Mereco, Inc. of West Warwick, RI. We are making an application to Oak Ridge National Lab to do neutron diffraction and X-ray scattering studies to further characterize the polymers. The goal is to make pliant plastics that can be formed into useable products that are toxic to various strains of resistant bacteria.