MOLECULAR DOCKING INSIGHTS INTO PROBIOTICS SAKACIN P AND SAKACIN A AS POTENTIAL INHIBITORS OF THE COX-2 PATHWAY FOR COLON CANCER THERAPY

MOHD ABDUL BAQI; KOPPULA JAYANTHI; RAMAN RAJESHKUMAR

doi:10.22159/ijap.2025v17i1.52476

Authors

MOHD ABDUL BAQI Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India
KOPPULA JAYANTHI Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India https://orcid.org/0009-0003-9358-4278
RAMAN RAJESHKUMAR Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52476

Keywords:

COX-2 enzyme, Molecular docking, MM-GBSA, ADME, Cancer, Probiotics, Bacteriocins, Anti-cancer agents

Abstract

Objective: This study aims to explore the interactions between probiotics-derived bacteriocins and the COX (cyclooxygenase) pathway, particularly focusing on the cancer-associated COX-2 (cyclooxygenase-2) enzyme (PDB ID: 6COX). The goal is to assess the potential of these bacteriocins as inhibitors of COX-2, investigating their possible anti-cancer effects through modulation of this key enzyme involved in cell growth and survival pathways.

Methods: Using the Glide module, the study first involved the molecular docking of bacteriocins. Next, an Absorption, Distribution, Metabolism, and Excretion (ADME) study was conducted using Qikprop. The Prime Molecular Mechanics Generalised Born Surface Area (MM-GBSA) method was used to calculate binding free energy.

Results: Four bacteriocins demonstrated significant binding affinity and interactions, including hydrogen and hydrophobic bonds, with key residues such as Tyr385, Ser530, Tyr355, Arg120, Phe518, and Leu352, in the associated COX-2 enzyme(PDB ID: 6COX). Among these, Sakacin P exhibited an excellent XP-docking score of-6.73 kcal/mol, indicating strong binding potential. Prime MM-GBSA analysis revealed promising binding affinities with ΔBind (-90.85 kcal/mol), ΔLipo (-64.81 kcal/mol), and ΔVdW (-46.34 kcal/mol). The ligand consistently interacted with residues Tyr355, and Arg120.

Conclusion: Sakacin P bacteriocin, characterized by functional groups including the primary amine (NH₂), and oxygen (O), demonstrates significant potential as a COX-2 enzyme inhibitor. This suggests its promising application as an anti-cancer agent, particularly for colon cancer.

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