9^{th European Chemistry Congress}

Biography

Biography: Daniel P Becker

Abstract

Boron neutron capture therapy (BNCT) is a non-invasive modality of treating brain tumors as well as head and neck tumors through delivery of a molecule containing ¹⁰B atoms to the tumor, which absorb a neutron under low-energy neutron irradiation to yield unstable ¹¹B nuclei that undergo fission to yield high energy alpha particles (⁴He nuclei) and high energy lithium-7 (⁷Li) nuclei that are limited in range to 5–9 µm, approximately the diameter of the target cell.  The challenge for improving BNCT is to target tumor cells to enable selective and efficient delivery of the ¹⁰B atoms.  Recognizing that matrix metalloproteinase (MMP) enzymes, especially gelatinases MMP-2 and MMP-2, as well as collagenase MMP-13, are upregulated in tumor cells, we selected to incorporate carborane clusters into scaffolds that are known to bind potently and selectively to these MMP enzymes.  Diaryl ether sulfone hydroxamate MMP inhibitors have served as clinical candidates for cancer treatment, and bear a piperidine substituent that is known to project from the MMP active site into solvent when the molecules are bound to MMP enzyme, thus enabling attachment of even very large dyes for imaging of tumors. Hence we have installed boron-rich carborane clusters to the piperidines nitrogen utilizing Click chemistry for attachement of the carborane moiety.  Herein we report the successful multistep synthesis of these BNCT agents and the potent MMP enzyme inhibition by these molecules as we proceed toward in vivo efficacy testing.