Autor según el artículo: Cuffaro, D; Gimeno, A; Bernardoni, BL; Di Leo, R; Pujadas, G; Garcia-Vallve, S; Nencetti, S; Rossello, A; Nuti, E
Departamento: Bioquímica i Biotecnologia
Autor/es de la URV: Garcia Vallve, Santiago / Pujadas Anguiano, Gerard
Palabras clave: Virtual screening Protein-ligand docking Osteoarthritis N-acyl hydrazones Mmp-13 inhibitors Matrix metalloproteinases protein-ligand docking osteoarthritis n-acyl hydrazones mmp-13 inhibitors isomerization highly potent discovery design
Resumen: Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1′ pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the µM range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new N-acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.
Áreas temáticas: Zootecnia / recursos pesqueiros Spectroscopy Saúde coletiva Química Psicología Physical and theoretical chemistry Organic chemistry Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Inorganic chemistry Geociências Farmacia Engenharias iv Engenharias ii Engenharias i Educação física Computer science applications Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Chemistry, multidisciplinary Catalysis Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: santi.garcia-vallve@urv.cat gerard.pujadas@urv.cat
Identificador del autor: 0000-0002-0348-7497 0000-0003-2598-8089
Fecha de alta del registro: 2024-08-03
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: International Journal Of Molecular Sciences. 24 (13):
Referencia de l'ítem segons les normes APA: Cuffaro, D; Gimeno, A; Bernardoni, BL; Di Leo, R; Pujadas, G; Garcia-Vallve, S; Nencetti, S; Rossello, A; Nuti, E (2023). Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization. International Journal Of Molecular Sciences, 24(13), -. DOI: 10.3390/ijms241311098
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2023
Tipo de publicación: Journal Publications
Repositori URV