Carborane-containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron Capture Therapy (BNCT)
Item
Title
Carborane-containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron Capture Therapy (BNCT)
Loyola Faculty Contributor
Daniel Becker
Link
List of Authors
Dr. Marlon R. Lutz Jr.; Sebastian Flieger; Andre Colorina; John Wozny; Prof. Dr. Narayan S. Hosmane; Prof. Dr. Daniel P. Becker
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.
Date
19-Oct-20
Publication Title
ChemMedChem
Publisher
Wiley
Identifier
10.1002/cmdc.202000470
Bibliographic Citation
Marlon R. Lutz, Jr., Sebastian Flieger, Andre Colorina, John Wozny, Narayan S. Hosmane, and Daniel P. Becker, Carborane-containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron Capture Therapy (BNCT), ChemMedChem 2020, http://dx.doi.org/10.1002/cmdc.202000470. Selected by Editors for issue Cover Art.