MOLECULAR DOCKING AND ADMET PROPERTIES OF NOVEL 5-METHYL-6AH-BENZO [4, 5] OXAZOLO [3,2-A]QUINOLIN-2-OL DERIVATIVES FOR THEIR ANTI-CANCER ACTIVITY

SIMPI MEHTA; POONAM KASWAN; POOJA RANJAN; SUDESH

doi:10.22159/ijap.2025v17i5.54488

Authors

SIMPI MEHTA DPG Institute of Technology and Management, Gurgaon-122004, India
POONAM KASWAN AISSMS Institute of Information Technology, Pune, India https://orcid.org/0000-0001-5138-7194
POOJA RANJAN Department of Chemistry, Hindu Girls College, Sonipat-131001, India
SUDESH Department of Chemistry, Research Scholar, Baba Mast Nath University, Rohtak-124001, India

DOI:

https://doi.org/10.22159/ijap.2025v17i5.54488

Keywords:

Benzo [4, 5]oxazolo[3,2-a]Quinolin-2-ol amine oxidase (AO), Molecular docking, Anticancer agents, Glide score, 2v5z, π–π stacking interactions, Hydrogen bonding, ADMET prediction, In silico drug design, Deprenyl, Biogenic amine deamination, Structure-based drug design (SBDD), Tumor progression, Pharmacokinetics

Abstract

Objective: This study aimed to design and evaluate a series of novel 5-Methyl-6aH-benzo [4,5]oxazolo [3,2-a]quinolin-2-ol derivatives as potential anticancer agents targeting the human amine oxidase (AO) enzyme.

Methods: Seventeen oxazole-based ligands were designed and subjected to molecular docking simulations using the crystallographic structure of human AO (PDB ID: 2v5z). GlideScore was used to assess binding affinity, and key molecular interactions were analyzed. Additionally, ADME-Toxicity properties were predicted to evaluate pharmacokinetic and safety profiles.

Results: Among the ligands, compounds 8 and 10 demonstrated the highest binding affinities, with GlideScores of –10.219 and –10.461 kcal/mol, respectively, significantly better than the reference drug R-(–)-Deprenyl (–6.205 kcal/mol). These ligands exhibited strong hydrophobic and π–π stacking interactions with active site residues PHE168, TRP119, and TYR435, indicating stable binding. ADME-Toxicity analysis revealed that all designed ligands had favorable pharmacokinetic profiles, including high oral absorption, low predicted toxicity, and acceptable blood-brain barrier permeability.

Conclusion: The results highlight the therapeutic potential of oxazole derivatives as effective scaffolds for developing new anticancer agents targeting amine oxidase, with compounds 8 and 10 emerging as promising lead candidates.

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