Chalcones are a class of \(\alpha\) , \(\beta\) -unsaturated ketones with significant pharmacological potential, including antiplatelet activity. Due to the limitations of drugs currently used as P2Y12 receptor inhibitors, such as clopidogrel, prasugrel, and ticagrelor – including metabolic activation requirements and interindividual variability, there is growing interest in investigating alternative compounds, such as chalcones, which may offer more different pharmacokinetic profiles and possible therapeutic safety. This study investigates the molecular and electronic characteristics of a chlorine-substituted chalcone, 3-(2-chlorophenyl)-1-[3-(2-oxo-2-phenyl-ethoxy)-phenyl]-propan-1-one (CPPO), to evaluate its potential as a P2Y12 receptor antagonist. Density functional theory calculations at the M06-2X/6–311 + + G(d,p) level of theory were employed to explore the molecular geometry, frontier molecular orbitals (FMOs), and global reactivity descriptors. Molecular electrostatic potential (MEP) maps, and Fukui functions were used to identify reactive sites. Pharmacokinetic properties and bioactivity predictions were assessed using SwissADME and PASS online servers. Molecular docking simulations with the P2Y12 receptor (PDB ID: 4PXZ) was conducted using GOLD Suite to evaluate binding affinity and interaction patterns. Pharmacophore analysis with the commercial P2Y12 ligands was performed using LigandScout 4.5. CPPO exhibited higher electrophilicity and polarizability than standard antiplatelet agents, with a favorable energy gap and molecular polarity index indicative of high reactivity and adaptability. MEP map and Fukui analyses identified regions prone to electrophilic, nucleophilic, and radical interactions. Bioactivity prediction indicated a high probability of antiplatelet activity, with favorable drug-likeness and low toxicity. Docking results associated with the pharmacophore analysis suggested that CPPO could fit well within the P2Y12 binding site, forming stable interactions with key amino acid residues. The integrated computational analysis indicates that CPPO is a promising P2Y12 receptor antagonist. Its electronic properties and predicted biological activity warrant further investigation through in vitro and in vivo studies to confirm its therapeutic potential as an antiplatelet agent.
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