Polyphenols are a large family of naturally occurring phytochemicals. Herein, oxyresveratrol was isolated from ethanolic crude extracts of Artocarpus lacucha Buch.-Ham., and chemically modified to derive its lipophilic analogues. Biological screening assays showed their inhibitory potency against cyclooxygenase-2 (COX-2) with very low cytotoxicity to the MRC-5 normal cell lines. At the catalytic site of COX-2, docking protocols with ChemPLP, GoldScore and AutoDock scoring functions were carried out to reveal hydrogen bonding interactions with key polar contacts and hydrophobic pi-interactions. For more accurate binding energetics, COX-2/ligand complexes at the binding region were computed in vacuo and implicit aqueous solvation using M06-2X density functional with 6-31G+(d,p) basis set. Our computational results confirmed that dihydrooxyresveratrol (4) is the putative inhibitor of human COX-2 with the highest inhibitory activity (IC₅₀ of 11.50 ± 1.54 µM) among studied non-fluorinated analogues for further lead optimization. Selective substitution of fluorine provides a stronger binding affinity; however, lowering the cytotoxicity of a fluorinated analogue to a normal cell is challenging. The consensus among biological activities, ChemPLP docking score and the binding energies computed at the quantum mechanical level is obviously helpful for identification of oxyresveratrol analogues as a putative anti-inflammatory agent.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide, and p53 dysfunction plays a significant role in its pathogenesis by impairing cell cycle control and apoptosis. This study aimed to elucidate the phytochemical composition and anticancer potential of extract of residue from clove hydrodistillation (Syzygium aromaticum, SA) and seed extract from Syzygium nervosum (SN). LC-DAD-MS/MS analysis identified gallic acid (2.68%) and ellagic acid (6.70%) as major constituents in SA, while SN contained gallic acid (0.26%), ellagic acid (3.06%), and 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) as major constituents. Both extracts exhibited potent antioxidant effects as evidenced by DPPH and ABTS assays. In vitro assays showed that SA and SN significantly inhibited the proliferation of HCT116 (p53 wild-type) colorectal cancer cells, with minimal effects on HT-29 (p53 mutant) cells. Apoptosis was confirmed in HCT116 via Annexin V-FITC/PI staining and increased caspase-3/7 activity. Cell cycle analysis revealed sub-G1 accumulation, accompanied by upregulated p21 and concurrently downregulated cyclin D1 expression, both hallmarks of p53-mediated checkpoint activation. These molecular effects were not observed in HT-29 cells. In conclusion, SA and SN extracts selectively induce apoptosis and cell cycle arrest in p53-functional CRC cells, likely mediated by their phenolic constituents. These findings support their potential as promising plant-derived therapeutic agents for targeted colorectal cancer treatment.