Anticancer Effects of Abietane Diterpene 7α-Acetoxy-6β-hydroxyroyleanone from Plectranthus grandidentatus 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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1807
JournalMolecules
Volume29
Issue number8
DOIs
Publication statusPublished - 16 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Funding

FundersFunder number
Fundação para a Ciência e a TecnologiaSFRH/BD/137671/2018

Keywords

  • Abietanes/chemistry
  • Antineoplastic Agents, Phytogenic/pharmacology
  • Antineoplastic Agents/pharmacology
  • Cell Line, Tumor
  • Computer Simulation
  • Diterpenes
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Plectranthus/chemistry

Fingerprint

Dive into the research topics of 'Anticancer Effects of Abietane Diterpene 7α-Acetoxy-6β-hydroxyroyleanone from Plectranthus grandidentatus and Its Semi-Synthetic Analogs: An In Silico Computational Approach'. Together they form a unique fingerprint.

Cite this