Document Type

Article

Publication Date

7-27-2020

Publication Title

ChemMedChem

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.

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

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Tuesday, July 27, 2021

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