Document Type
Article
Publication Date
7-27-2020
Publication Title
ChemMedChem
Volume
15
Pages
1897-1908
Publisher Name
Wiley, European Chemical Societies Publishing
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.
Recommended Citation
Lutz, Marlon R. Jr; Flieger, Sebastian; Colorina, Andre; Wozny, John; Hosmane, Narayan S.; and Becker, Daniel P. Ph.D.. Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT). ChemMedChem, 15, : 1897-1908, 2020. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.1002/cmdc.202000470
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright Statement
© Wiley‐VCH GmbH, 2020.
Comments
Author Posting © Wiley‐VCH GmbH, 2020. This is the author's version of the work. It is posted here by permission of Wiley‐VCH GmbH for personal use, not for redistribution. The definitive version was published in ChemMedChem, July 2020. https://doi.org/10.1002/cmdc.202000470