Theoretical investigation of vitexin/isovitexin interactions with the [Zn-(His)3]2+ containing MMP-9 active site using DFT methods
Chemical Papers, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s11696-026-04956-6
- Dergi Adı: Chemical Papers
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Chemical Abstracts Core, Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: DFT, Flavonoid inhibition, Isovitexin, MMP-9, Vitexin, Zinc coordination
- İstanbul Ticaret Üniversitesi Adresli: Evet
Özet
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases essential for extracellular matrix remodeling and implicated in numerous pathological conditions. The catalytic activity of MMPs depends on a conserved zinc-binding motif in which three histidine residues coordinate the catalytic Zn2+ ion. Although the inhibitory interactions of vitexin and isovitexin—two C-glycosyl flavonoids abundant in Ficus deltoidei extracts—with MMP-9 have been demonstrated experimentally, the underlying molecular mechanism has not been theoretically characterized. In the present study, the MMP-9 active site was modeled as the [Zn-(His)3]2+ ligand, and the interaction mechanisms of vitexin and isovitexin were investigated by density functional theory (DFT) at the B3LYP/6-31G(d,p) level. The results demonstrate that Zn2+ forms stable, penta-coordinated complexes through coordination with three histidine nitrogen atoms and the phenolic oxygen atoms of the flavonoid ligands. Natural Bond Orbital (NBO) charge analysis reveals that vitexin induces a more substantial decrease in the positive charge of the Zn(II) center than isovitexin, indicating stronger coordination. Time-dependent DFT (TD-DFT) calculations show that complex formation significantly modulates electronic transition energies, with the isovitexin complex exhibiting enhanced charge-transfer character in polar environments. These findings are consistent with experimental data and provide molecular-level insight into Zn(II)-dependent MMP-9 inhibition by flavonoid compounds.