Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR.
Maria Galvez-LlompartJesús HierrezueloMariluz BlascoRiccardo ZanniJorge GalvezAntonio de VicenteAlejandro Pérez-GarcíaDiego RomeroPublished in: Journal of enzyme inhibition and medicinal chemistry (2024)
Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure-activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (-) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.
Keyphrases
- biofilm formation
- candida albicans
- structure activity relationship
- antimicrobial resistance
- pseudomonas aeruginosa
- staphylococcus aureus
- human health
- silver nanoparticles
- molecular docking
- escherichia coli
- gram negative
- risk assessment
- endothelial cells
- molecular dynamics
- healthcare
- cystic fibrosis
- cancer therapy
- anti inflammatory
- high resolution
- emergency department
- photodynamic therapy
- essential oil
- high throughput
- radiation therapy
- multidrug resistant
- drinking water
- adverse drug
- single cell
- combination therapy
- induced pluripotent stem cells
- single molecule
- electronic health record
- pluripotent stem cells