COMPUTATIONAL SCREENING OF NATURAL COMPOUNDS AS POTENTIAL AURORA A KINASE INHIBITORS FOR LEUKEMIA CANCER TREATMENT: A MULTI-STEP IN SILICO APPROACH

Objective: The overexpression of aurora a kinase is associated with leukaemia as it is an essential regulator of mitotic progression, rendering it a promising therapeutic target. This study employed a multi-step in silico strategy that incorporated computational screening, molecular docking, Density Functional Theory (DFT) analysis, free energy calculations (MM-GBSA), and Molecular Dynamics (MD) simulations to evaluate the potential of natural compounds as Aurora A kinase inhibitors. Methods: An initial virtual screening of 3,093 natural compounds from the Selleckchem library was performed. Drug-likeness was assessed using Lipinski’s Rule of Five, which filters compounds based on key pharmacokinetic parameters: molecular weight (≤ 500 Da), LogP (≤ 5), hydrogen bond donors (≤ 5), and hydrogen bond acceptors (≤ 10). A total of 2,045 compounds that satisfied all these criteria were selected for further analysis and bioactivity evaluation. Results: After ML-based QSAR screening, molecular docking identified 683 ligands with binding affinities of ≤-6.0 kcal/mol. Out of all natural compounds, PubChem CID: 94381 (Coumarin 7) and PubChem CID: 1830 (7-Iodo-7-deaza-D-guanosine) showed minimal RMSD (0.1-0.3 nm), and high hydrogen bonding (2-6 stable contacts) during the 100 ns MD simulations, suggesting stable binding within the aurora A kinase active site. The strong binding affinity of MM-GBSA was further validated by the binding free energy calculations, which showed favourable values of ΔG =-27.93 kcal/mol (94381) and -27.50 kcal/mol (1830). Conclusion: Further, with a dipole moment of 2.80 D, 1830 had great electrical stability, and the lowest HOMO-LUMO gap (-0.1580 eV/-0.1311 eV) was observed in 94381, according to DFT calculations, which indicated significant reactivity. Additionally, synthetic accessibility scores of 3.19 and 4.00, respectively, and iLOGP (integrative octanol–water partition coefficient) values of 2.46 (94381) and 1.57 (1830), both compounds showed ideal drug-like characteristics and may be developed further.

• Publication year

  2025

• Venue

  International Journal of Applied Pharmaceutics

• Publication date

  2025-11-07

• Fields of study

  Not labeled

• Identifiers
  DOI 10.22159/ijap.2025v17i6.55338
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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