Design and synthesis of water-soluble and potent MMP-13 inhibitors with activity in human osteosarcoma cells
Keywords: 
MMP-13 inhibitors
Metalloproteinases
Osteoarthritis
Molecular modeling
RMN
Organic synthesis
Issue Date: 
2021
ISSN: 
1422-0067
Note: 
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Citation: 
Zapico, J. M.; Acosta, L.; Pastor, M.; et al. "Design and synthesis of water-soluble and potent MMP-13 inhibitors with activity in human osteosarcoma cells". International Journal of Molecular Sciences. 22 (18), 2021, 9976
Abstract
Osteoarthritis is a degenerative disease, often resulting in chronic joint pain and commonly affecting elderly people. Current treatments with anti-inflammatory drugs are palliative, making the discovery of new treatments necessary. The inhibition of matrix metalloproteinase MMP-13 is a validated strategy to prevent the progression of this common joint disorder. We recently described polybrominated benzotriazole derivatives with nanomolar inhibitory activity and a promising selectivity profile against this collagenase. In this work, we have extended the study in order to explore the influence of bromine atoms and the nature of the S1 ' heterocyclic interacting moiety on the solubility/selectivity balance of this type of compound. Drug target interactions have been assessed through a combination of molecular modeling studies and NMR experiments. Compound 9a has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells.

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