2. Academic Validation
  3. Carborane-Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron-Capture Therapy (BNCT)

Carborane-Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron-Capture Therapy (BNCT)

  • ChemMedChem. 2020 Oct 19;15(20):1897-1908. doi: 10.1002/cmdc.202000470.
Marlon R Lutz Jr 1,  Sebastian Flieger 2,  Andre Colorina 3,  John Wozny 4,  Narayan S Hosmane 4,  Daniel P Becker 2
Affiliations

Affiliations

  • 1 Biosynthetic Technologies, 6320 Intech Way, Indianapolis, IN 46278, USA.
  • 2 Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL 60660, USA.
  • 3 Regis Technologies, Inc., 8210 Austin Ave., Morton Grove, Illinois 60053, USA.
  • 4 Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA.
PMID: 32720425 DOI: 10.1002/cmdc.202000470
Abstract

Based on the previously reported potent and selective sulfone hydroxamate inhibitors SC-76276, SC-78080 (SD-2590), and SC-77964, potent MMP inhibitors have been designed and synthesized to append a boron-rich carborane cluster by employing click chemistry to target tumor cells that are known to upregulate gelatinases. Docking against MMP-2 suggests binding involving the hydroxamate zinc-binding group, key H-bonds by the sulfone moiety with the peptide backbone residues Leu82 and Leu83, and a hydrophobic interaction with the deep P1' pocket. The more potent of the two triazole regioisomers exhibits an IC50 of 3.7 nM versus MMP-2 and IC50 of 46 nM versus MMP-9.

Keywords

boron neutron capture therapy (BNCT); carborane; matrix metalloproteinases (MMPs).

Figures
Products