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 IscaPrzemysław SitarekAnna Merecz-SadowskaMagdalena MaleckaMonika OwczarekJoanna WieczfinskaRadosław ZajdelPaweł NowakPatrícia RíjoTomasz KowalczykPublished in: Molecules (Basel, Switzerland) (2024)
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.
Keyphrases
- molecular docking
- molecular dynamics simulations
- network analysis
- human health
- papillary thyroid
- molecular dynamics
- oxidative stress
- binding protein
- single cell
- signaling pathway
- risk assessment
- dna binding
- mass spectrometry
- squamous cell
- transcription factor
- squamous cell carcinoma
- climate change
- ms ms
- cell death
- amino acid
- monte carlo