ADME/drug-likeness and functional properties of Punica granatum seeds supported with molecular docking, GC-MS and LC-MS/MS analysis.

In this study, phytochemical fingerprint and biological activities of Punica granatum L. seed extract (Pugex) were investigated. The phytochemical constituents were determined by LC-MS /MS and GC-MS analyses. The biological activity of the extract was investigated by anti-microbial, anti-genotoxic, anti-proliferative, anti-cholinesterase and anti-diabetic activity. All biological activities experimentally demonstrated in vitro were also investigated by molecular docking. The drug-likeness properties of selected phytochemicals were evaluated using the Molinspiration tool. The highest amounts of 2-oxatricyclo[4.3.1.0(3,8)]decane, 2-heptenal, 2-propyl- and 1 H-indene-1-one, gallic acid and ellagic acid were detected as major constituents in LC-MS/MS and GC-MS. Pugex showed a broad spectrum of anti-microbial activity by forming inhibition zones against all tested bacteria, with anti-genotoxic activity ranging from 53.31% to 74.48% against various chromosomal aberrations and anti-proliferative activity by reducing cell proliferation by 15.6%. Pugex inhibited α-glucosidase activity between 30.2% and 61.3% and α-amylase activity between 27.4% and 56.7%. The anti-cholinesterase activity of the seeds, which showed AChE inhibition up to 67.8% and BChE inhibition up to 79.8%, was associated with the essential oils they contained. The biological activities of the seeds were also confirmed by in silico interactions, and possible mechanisms were predicted, and drug likeness data provide preliminary information on the availability of phytochemicals for drugs. Drug-likeness features of the major components-2-Oxatricyclo [4.3.1.0(3,8)]decane, ellagic acid, gallic acid, and pulegone-were investigated. The logP values of all phytochemicals were found to be below 5, indicating compliance with Lipinski's rule of five and suggesting their potential to cross biological membranes. Furthermore, phytochemicals with a total polar surface area below 140 Å are expected to exhibit improved intestinal absorption. Based on these findings, the phenolic acid derivatives evaluated in this study are anticipated to be well absorbed through the intestinal tract.