| Title: |
Design and Synthesis ofWater-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells. |
| Authors: |
Zapico Rodríguez, José María.; Acosta, Lourdes.; Pastor, Miryam.; Rangasamy, Loganathan.; Márquez-Cantudo, Laura.; Coderch, Claire.; Ortín, Irene.; Nicolau-Sanus, María.; Puchades-Carrasco, Leonor.; Pineda-Lucena, Antonio.; Majali-Martinez, Alejandro.; Ramos Álvarez, María del Pilar.; Pascual-Teresa Fernández, Beatriz de.; Ramos González, Ana. |
| Publication Year: |
2021 |
| Subject Terms: |
Síntesis orgánica; MMP-13 inhibitors; Metalloproteinases; Molecular modeling; Osteoarthritis; RMN; Organic synthesis |
| Description: |
International Journal Molecular Sciences, e-ISSN 1422-0067, 2021, 22, 9976 ; 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 S10 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
This research was funded by RTI2018-093539-B-I00 (MICIU/FEDER, UE). Laura MarquezCantudo thanks Universidad San Pablo CEU and Banco Santander for a Young Researcher contract. Part of the equipment used in this work was co-funded by the Generalitat Valenciana and European Regional Development Fund (FEDER) funds (PO FEDER of Comunitat Valenciana 2014–2020) and Community of Madrid (S2017/BMD-3864). This project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie-Sklodowska-Curie grant agreement number DUALITY 746225.; 000000726403; http://hdl.handle.net/10637/13381; https://doi.org/10.3390/ijms22189976 |
| DOI: |
10.3390/ijms22189976 |
| Availability: |
http://hdl.handle.net/10637/13381; https://doi.org/10.3390/ijms22189976 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es |
| Accession Number: |
edsbas.4C40B137 |
| Database: |
BASE |