Molecular docking reveals curcumin and catechin as potent inhibitors of histamine N-Methyltransferase (HNMT) and its T۱۰۵I and L۲۰۸P variants

Background: Histamine plays a crucial role in regulating diverse physiological and pathophysiological functions, including gastric acid secretion, vasodilation, and bronchoconstriction. As a neurotransmitter, it is also implicated in allergic reactions, contributing to symptoms such as itching, sneezing, and inflammation. Given the potential adverse effects of histamine activity, antihistamines are frequently prescribed to mitigate its effects. However, the associated side effects of these drugs have prompted researchers to investigate natural alternatives, such as curcumin from turmeric and catechins from green tea. This study investigates the potential effect of curcumin and catechin on the histamine N-methyltransferase (HNMT) receptor and its T۱۰۵I and L۲۰۸P mutant variants. Methods: Molecular docking was employed to analyze ligand-receptor interactions. The protein structure was obtained from the Protein Data Bank (PDB), and ligands were retrieved from PubChem. Ligand structures were optimized using Avogadro software, and docking studies were subsequently performed using AutoDock Tools and the Vina algorithm. Results: Molecular docking studies have demonstrated strong binding affinities of catechin and curcumin to the target protein, with binding energies of -۸.۵ and -۸.۴ kcal/mol, respectively, which is more than twice the binding affinity of histamine (-۴.۰ kcal/mol). Analysis of docking results with variant proteins revealed a slight reduction in ligand binding energies compared to the normal protein. These findings suggest that both catechin and curcumin hold promise as potential therapeutic agents for patients with the studied variants of the target protein. Furthermore, docking analysis revealed key stabilizing interactions, including π-π stacking and hydrogen bonding. Conclusion: Phe۲۴۳ is a key binding site residue in HNMT, showing consistent strong interactions with all tested ligands. Its structural flexibility enables effective binding to compounds like catechin and curcumin, making it a prime target for designing new HNMT inhibitors.

کلیدواژه ها:

Curcumin ، Catechin ، Histamine N-Methyltransferase ، Molecular Docking