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This study aims to isolate the active constituents of Pyrus pyrifolia Nakai fruits using a bioassay-guided fractionation approach, test their activity in vitro against key enzymes for metabolic disorders, and support it with molecular docking simulations. The antioxidant potential of the methanolic extract (ME), its polar (PF), and non-polar fractions (NPF), along with the inhibitory activity against α-glucosidase, α-amylase, lipase, angiotensin I converting enzyme (ACE), renin, inducible nitric oxide synthase (iNOS), and xanthine oxidase (XO) were assessed. The PF exhibited the highest antioxidant and enzyme inhibitory activity. Purification of PF yielded rutin, isoquercitrin, isorhamnetin-3-O-β-D-glucoside, chlorogenic acid, quercetin, and cinnamic acid. HPLC-UV analysis of the PF allowed for the quantification of 15 phenolic compounds, including the isolated compounds. Cinnamic acid was the most powerful antioxidant in all assays and potent enzyme inhibitor against the tested enzymes (α-glucosidase, α-amylase, lipase, ACE, renin, iNOS, and XO). Additionally, it showed high affinity to target α-glucosidase and ACE active sites with high docking scores (calculated total binding free energy (ΔGbind) -23.11 kcal/mol and − 20.03 kcal/mol, respectively]. A 20-ns molecular dynamics simulation using MM-GBSA analysis revealed a stable conformation and binding patterns in a stimulating environment of cinnamic acid. Interestingly, the isolated compounds’ dynamic investigations including RMSD, RMSF, and Rg demonstrated a stable ligand − protein complex to the active site of iNOS with ΔGbind ranging from − 68.85 kcal/mol to -13.47 kcal/mol. These findings support the notion that P. pyrifolia fruit is a functional food with multifactorial therapeutic agents against metabolic syndrome-associated diseases.

In this study, new amino heterocyclic cellulose derivatives were prepared. Dialdehyde cellulose was functionalized by Schiff base reaction with (E)-2-(4-(dimethylamino) benzylidene)-4-oxo-4-phenylbutanehydrazide, (E)-2-((1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-4-phenylbutane hydrazide, and thiophene-2-carbohydrazide. The prepared derivatives were characterized and confirmed by Fourier-transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray, and Thermo gravimetric analysis. Additionally, antimicrobial activity of all derivatives was assessed as well as antitumor activity. Results revealed that, all derivatives have potential antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Cryptococcus neoformance, Aspergillus niger, A. fumigatus. Additionally, (E)-2-(4-(dimethylamino) benzylidene)-4-oxo-4-phenylbutanehydrazide and (E)-2-((1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-4-phenylbutanehydrazide cellulose compounds have good antitumor activities against Hep G2 and MCF7 cancerous cell lines without any effects on Wi38 normal cell line. Molecular dynamics study revealed that (E)-2-(4-(dimethylamino) benzylidene)-4-oxo-4-phenylbutanehydrazide and (E)-2-((1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-4-phenylbutanehydrazide cellulose derivatives have selectively target the ATP binding pocket residues. Identification of these ATP binding site residues and their crucial roles could provide the structure basis for understanding c-Kit kinase auto-inhibition