MOLECULAR DOCKING INSIGHTS INTO PROBIOTICS AS POTENTIAL INHIBITORS OF THE PI3K PATHWAY FOR COLON CANCER THERAPY

MOHD ABDUL BAQI; KOPPULA JAYANTHI; RAMAN RAJESHKUMAR

doi:10.22159/ijap.2025v17i1.52436

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 https://orcid.org/0000-0001-5498-7929

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52436

Keywords:

Phosphoinositide 3-kinases (PI3Ks), Molecular docking, MM-GBSA, ADME, Cancer, Probiotics, Bacteriocins, Anti-cancer agents

Abstract

Objective: This study investigates the interactions of probiotics-derived bacteriocins with Phosphoinositide 3-kinases (PI3Ks), a key enzyme involved in cell growth and survival pathways, with a focus on the cancer-associated PI3K pathway (PDB ID: 1E8X). The aim is to explore the anti-cancer potential of these bacteriocins as inhibitors of the PI3K catalytic subunit.

Methods: Using the Glide module, the study first involved 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: Five bacteriocins demonstrated significant binding affinity and interactions, including hydrogen and hydrophobic bonds, with key residues such as Tyr867, Trp812, Asp950, Asn951, Lys802, Lys890, Lys833, Val882, Ser806, Thr886, and Gln893 in the PI3K catalytic subunit (PDB ID: 1E8X). Among these, Plantaricin D exhibited an excellent XP-docking score of-7.47 kcal/mol, indicating strong binding potential. Prime MM-GBSA analysis revealed promising binding affinities with ΔBind (-92.85 kcal/mol), ΔLipo (-65.81 kcal/mol), and ΔVdW (-47.34 kcal/mol). The ligand consistently interacted with residues Asp950, Lys890, Gln893, Ser894, Thr887, Ala885, Tyr757, Asp758, Lys802, and Val759.

Conclusion: Plantaricin D bacteriocin, characterized by functional groups including the primary amine (NH₂), carbonyl (C=O), hydroxide (OH), and oxygen (O), demonstrates significant potential as a PI3K inhibitor. This suggests its promising application as an anti-cancer agent, particularly for colon cancer.

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