Portal de investigación
Design and Synthesis of Water-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Zapico, JM
- Acosta, L
- Pastor, M
- Rangasamy, L
- Marquez-Cantudo, L
- Coderch, C
- Ortin, I
- Nicolau-Sanus, M
- Pineda-Lucena, A
- Majali-Martinez, A
- Ramos, P
- de Pascual-Teresa, B
- Ramos, A
Grupos
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.
Datos de la publicación
- ISSN/ISSNe:
- 1661-6596, 1661-6596
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.3390/ijms22189976
- PubMed:
- 34576138
- Factor de Impacto:
- 1,176 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES MDPI AG
Citas Recibidas en Web of Science: 5
Documentos
- No hay documentos
Filiaciones
Keywords
- MMP-13 inhibitors; metalloproteinases; osteoarthritis; molecular modeling; RMN; organic synthesis
Financiación
Proyectos y Estudios Clínicos
HERRAMIENTAS DE RMN PARA EL DESARROLLO DE UNA PLATAFORMA PARA LA IDENTIFICACIÓN DE DIANAS, LA EVALUACIÓN DE FÁRMACOS Y LA PERSONALIZACIÓN DE TRATAMIENTOS BASADA EN APROXIMACIONES METABOLÓMICAS
Investigador Principal: ANTONIO PINEDA LUCENA
SAF2014-53977-R . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD . 2015
Estudio del papel de la heparanasa en la resistencia a los tratamientos para el mieloma múltiple.
GV/2017/ . 2018
New integrative analysis of genetic vulnerabilities in advanced prostate cancer for the identification of novel pharmaceutically relevant protein targets
Investigador Principal: LEONOR PUCHADES CARRASCO
GV/2021/154 . CONSELLERIA DE INNOVACIÓN, UNIVERSIDADES, CIENCIA Y SOCIEDAD DIGITAL . 2021
Cita
Zapico JM,Acosta L,Pastor M,Rangasamy L,Marquez L,Coderch C,Ortin I,Nicolau M,PUCHADES L,Pineda A,Majali A,Ramos P,de Pascual B,Ramos A. Design and Synthesis of Water-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells. Int. J. Mol. Sci. 2021. 22. (18):9976. IF:6,208. (1).