Autor segons l'article: Cuffaro, Doretta; Gimeno, Aleix; Bernardoni, Bianca Laura; Di Leo, Riccardo; Pujadas, Gerard; Garcia-Vallve, Santiago; Nencetti, Susanna; Rossello, Armando; Nuti, Elisa
Departament: Bioquímica i Biotecnologia
Autor/s de la URV: Garcia Vallve, Santiago / Gimeno Vives, Aleix / Pujadas Anguiano, Gerard
Paraules clau: Virtual screening; Protein-ligand docking; Osteoarthritis; N-acyl hydrazones; Mmp-13 inhibitors; Matrix metalloproteinases; Matrix metalloproteinase inhibitors; Matrix metalloproteinase 13; Humans; Collagen; Cartilage, articular; protein-ligand docking; osteoarthritis; n-acyl hydrazones; mmp-13 inhibitors; isomerization; highly potent; discovery; design
Resum: 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.
Àrees temàtiques: 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
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: aleix.gimeno@urv.cat; aleix.gimeno@urv.cat; santi.garcia-vallve@urv.cat; gerard.pujadas@urv.cat
Data d'alta del registre: 2025-03-22
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://www.mdpi.com/1422-0067/24/13/11098
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Referència a l'article segons font original: International Journal Of Molecular Sciences. 24 (13): 11098-
Referència de l'ítem segons les normes APA: Cuffaro, Doretta; Gimeno, Aleix; Bernardoni, Bianca Laura; Di Leo, Riccardo; Pujadas, Gerard; Garcia-Vallve, Santiago; Nencetti, Susanna; Rossello, Ar (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), 11098-. DOI: 10.3390/ijms241311098
DOI de l'article: 10.3390/ijms241311098
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2023
Tipus de publicació: Journal Publications
Repositori URV