IN-SILICO COMBINATORIAL INHIBITION EFFECT ANALYSIS OF NSAIDS AGAINST MMP-9 FOR THE TREATMENT OF CANCER

Overexpression of Matrix metalloproteinases (MMPs) in cancers promotes tumor by degrading the barrier of extracellular matrix and angiogenesis. MMP-9 plays a major role in the progression of cancers by enhancing migration, cell survival, angiogenesis, epithelial-to-mesenchymal transition, immune response induction, and tumor microenvironment formation thus, it is considered as a lead drug target to treat cancer. NSAIDs or Nonsteroidal anti-inflammatory drugs have been widely investigated for their effectiveness in different cancer types but promising candidates for clinical use are still halfway. The present study aims to investigate a combination of NSAIDs that can convey high-potential structural inhibition against MMP-9 utilizing a molecular docking-based in-silico approach. A thorough literature survey followed by ADMET analysis provided the best NSAID candidates covering diverse chemical space for the analysis. Molecular docking of NSAIDs with MMP-9 individually proved oxaprozin and piroxicam as best candidates for structural inhibition of MMP-9. Combination docking gave a high binding energy of -12.98 kcal/mol for the synergistic inhibitory effect of oxaprozin and piroxicam against MMP-9. Thus, further in-vitro analysis can provide a highly effective NSAID combination to treat the pathologies of cancer in an efficient manner.