DefinePK

Abstract

In silico drug repurposing has emerged as a promising methodology for the identification of novel therapeutic applications for pre-existing pharmaceuticals. This investigation explores the efficacy of eight selected third-generation cephalosporin antibiotics, as potential inhibitor of matrix metalloproteinase-2 (MMP-2) in ovarian cancer. MMP-2 is recognized for its pivotal role in tumor progression and metastasis, rendering it a compelling target for oncological treatment. We assessed the binding affinity and stability of selected cephalosporins with MMP-2 using molecular docking and molecular dynamics simulations. Our findings indicate that only Cefoperazone demonstrates robust binding interactions (∆G -8.1 Kcal/mol) within the active site of MMP-2, suggesting its viability as an effective inhibitor. Furthermore, MD simulations (duration 10 mins) using normal mode analysis (NMA) revealed that the interactions between MMP-2 and Cefoperazone are exceptionally stable under virtual physiological conditions. The low eigenvalue (1.513588e−04) and B-factor further support the stability of the docked complex. Elastic network model analysis indicates that the docked protein molecule atoms are interconnected by flexible springs, suggesting appropriate molecular motion in the vicinity of the binding site. Consequently, these findings offer novel insights into cefoperazone as a potential candidate for MMP-2 inhibition in the treatment of ovarian cancer. This research also demonstrates the efficacy of in silico methodologies in drug repurposing and paves the way for developing targeted therapeutic strategies in the management of ovarian cancer.