Molecules (Apr 2024)

Anticancer Effects of Abietane Diterpene 7α-Acetoxy-6β-hydroxyroyleanone from <i>Plectranthus grandidentatus</i> and Its Semi-Synthetic Analogs: An In Silico Computational Approach

  • Vera M. S. Isca,
  • Przemysław Sitarek,
  • Anna Merecz-Sadowska,
  • Magdalena Małecka,
  • Monika Owczarek,
  • Joanna Wieczfińska,
  • Radosław Zajdel,
  • Paweł Nowak,
  • Patricia Rijo,
  • Tomasz Kowalczyk

DOI
https://doi.org/10.3390/molecules29081807
Journal volume & issue
Vol. 29, no. 8
p. 1807

Abstract

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The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand–protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819–0.879). Strategic modifications altered HOMO–LUMO gaps (3.39–3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.

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