Deregulation and changes in energy metabolism are emergent and important biomarkers of cancer cells. The uptake of hexoses in cancer cells is mediated by a family of facilitative hexose membrane-transporter proteins known as Glucose Transporters (GLUTs). In the clinic, numerous breast cancers do not show elevated glucose metabolism (which is mediated mainly through the GLUT1 transporter) and may use fructose as an alternative energy source. The principal fructose transporter in most cancer cells is GLUT5, and its mRNA was shown to be elevated in human breast cancer. This offers an alternative strategy for early detection using fructose analogs. In order to selectively scout GLUT5 binding-pocket requirements, we designed, synthesized and screened a new class of fructose mimics based upon the 2,5-anhydromannitol scaffold. Several of these compounds display low millimolar IC50 values against the known high-affinity 18F-labeled fructose-based probe 6-deoxy-6-fluoro-D-fructose (6-FDF) in murine EMT6 breast cancer cells. In addition, this work used molecular docking and molecular dynamics simulations (MD) with previously reported GLUT5 structures to gain better insight into hexose–GLUT interactions with selected ligands governing their preference for GLUT5 compared to other GLUTs. The improved inhibition of these compounds, and the refined model for their binding, set the stage for the development of high-affinity molecular imaging probes targeting cancers that express the GLUT5 biomarker.

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A series of new 2,4-disubstituted phenylhydrazonopyrazolone and isoxazolones have been synthesized and evaluated for antibacterial activity. These compounds incorporated the bioactive moieties 3-methyl isoxazolone and 3-methyl pyrazolone. Based on the preliminary results, evaluation of these new compounds as potential antimicrobial agents revelead that four of them which incorporate the isoxazolone moiety exhibited selective antimicrobial activity against Gram-positive bacteria with MICs for S. aureus in the 50-100 mgmL À1 range. Additionally, docking studies were performed in order to explore the possible binding poses in the MurB protein of S. aureus and the results were correlated to the antimicrobial results reported herein.