IN SILICO IDENTIFICATION OF PHYTOCHEMICAL INHIBITORS TARGETING MMP-9 AND IL-18 IN TAKAYASU ARTERITIS

Abstract

Takayasu arteritis (TAK) is an autoimmune, inflammatory-driven, enduring, large-vessel vasculitis characterized by structural vascular stenosis and aneurysm formation. The major mediators of extracellular matrix breakdown and inflammatory signalling are matrix metalloproteinase-9 (MMP-9) and interleukin-18 (IL-18); there is a lack of systematic assessment of phytochemicals as dual inhibitors of these factors. The aim of the study was to discover phytochemical inhibitors with a dual potential of MMP-9 and IL-18, with strong binding capacity and pharmacokinetic viability to be used as a prospective therapeutic agent in TAK. A total of sixteen bioactive phytochemicals were obtained from PubChem and evaluated in silico. High-resolution crystal structures of MMP-9 (PDB: 1L6J) and IL-18 (PDB: 2VXT) were used in molecular docking. Docking identified seven top-ranking compounds, demonstrating consistently high binding affinities across both targets, stabilized through hydrogen bonding, hydrophobic interactions, and π-stacking within structurally relevant pockets. SwissADME profiling has shown favourable pharmacokinetics of conformity to Lipinski Rule of Five and high gastrointestinal absorption and appropriate bioavailability, which favour their drug-likeness. The occupancy of ligands in the functional binding cavities was confirmed by CASTp analysis. These results suggest that quercetin and luteolin might be considered as possible dual-target drugs, capable of curing inflammatory signalling and extra-cellular matrix remodelling during TAK. Future research can confirm the efficacy, pharmacodynamics, and safety of these phytochemicals in vitro and in vivo and develop them as potential therapeutics.