Bioactive compounds from marine algae targeting MMP-9: A computational approach to rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a chronic autoimmune systemic inflammatory condition that significantly damages bone and cartilage, leading to severe joint deformities. Matrix metalloproteinase(s) (MMP-9) plays a significant role in both the pathogenesis and management of RA, and its status as a biomarker and a target for inhibition is important in understanding and treating the disease. This work aims to examine the interactions between the molecules of MMP-9 and bioactive compounds derived from marine algae using molecular docking and absorption, distribution, metabolism, excretion, and toxicity investigations. Docking results were assessed using Glide gscore, the top 5 compounds (6,6-Bieckol, Dieckol, Lophocladine B, Sargachromanol E, and Porphyran) docked against protein receptors were chosen. The selected compounds had binding affinities that varied from -8.523 to -6.327 kcal/mol, and the selected compounds also had undergone absorption, distribution, metabolism, excretion, and toxicity analysis. Density functional theory analysis was conducted against finalized compound, Lophocladine B, with HOMO-LUMO gaps of 4.235 and 5.275 eV, respectively, confirming electronic stability and binding-relevant reactive sites consistent with its predicted MMP-9 inhibition. It was discovered that only Lophocladine B met the selection criteria, so this compound was subjected to molecular dynamics simulations for stability analysis. Moreover, the docking studies were supported by redocking validation of the native inhibitor, heavy-atom root mean square deviation, benchmarking with a known inhibitor, and molecular dynamics simulations along with a replication run. The results of the study imply that these substances might ultimately be employed to treat rheumatoid arthritis. Although this study only included computer validations, in vitro investigations are needed to convert these potential inhibitors into medicinal products.