Maturity-dependent enzyme inhibition in grape seeds. Urease, α-amylase, and lipase inhibitory activities with lipase docking insights and antimicrobial properties

This study investigated the enzyme inhibitory, antimicrobial, and molecular docking properties of grape seed extracts obtained from three Algerian grape cultivars—Sabel, Red Globe, and Cardinal—harvested at different ripening stages. The extracts demonstrated strong inhibitory activity against urease, α-amylase, and lipase, with variability depending on both cultivar and maturation stage. Cardinal seeds displayed the most potent urease inhibition ((IC₅₀ = 3.37 μg/mL) at the BV stage, surpassing the reference thiourea (7.27 ± 1.04 μg/mL), whereas α-amylase inhibition was consistently higher than the commercial inhibitor acarbose with the best activity recorded in RG at repining stage (IC₅₀ = 31.94 μg/mL). Lipase inhibition was markedly enhanced at the late ripening stage for Sabel and Cardinal, highlighting maturation as a critical determinant of bioactivity. Docking simulations revealed that catechin, luteolin, and resveratrol established stable interactions with catalytic residues of pancreatic lipase, supporting the in vitro findings. ADME/Tox predictions confirmed favorable pharmacokinetic properties and low toxicity for most compounds. Antimicrobial assays further demonstrated cultivardependent activity against multidrug-resistant Escherichia coli, Candida albicans, and Aspergillus niger, with Cardinal and Red Globe showing the strongest effects with the highest inhibition zones up to 19 mm against multidrug-resistant E. coli. Together, these results highlight grape seeds as a significant reservoir of bioactive substances with possible uses in managing metabolic disorders, infections, and obesity.