Abietane diterpenoids exhibit a wide range of bioactivities, including antimicrobial, anticancer, anti-inflammatory, and antiviral effects. The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy), extracted from Plectranthus grandidentatus, has exhibited significant cytotoxic effects against a sereral cancer cell line. To improve its anticancer efficacy, several semi-synthetic derivatives of Roy were developed and subjected to extensive in silico evaluation.

This computational assessment involved the prediction of pharmacokinetic parameters, including absorption, distribution, metabolism, excretion, and toxicity (ADMET), to determine drug-likeness and safety profiles. The potential anticancer activity of each compound was estimated using PASS (Prediction of Activity Spectra for Substances), while density functional theory (DFT) was employed to analyze molecular stability and electronic properties. Furthermore, molecular docking and molecular dynamics (MD) simulations were conducted to assess the interaction strength and stability of the derivatives with cancer-associated protein targets.

ADMET modeling suggested that the compounds possessed favorable pharmacokinetic characteristics and acceptable toxicity levels. DFT-based quantum chemical calculations revealed alterations in HOMO–LUMO energy gaps (ranging from 3.39 to 3.79 eV) and provided insights into global reactivity descriptors. PASS analysis predicted strong anticancer potential, with probability scores between 0.819 and 0.879.

Docking studies indicated strong binding affinities toward key oncogenic targets, including cyclin-dependent kinases (CDKs), BCL-2, caspases, receptor tyrosine kinases, and p53, with MD simulations confirming the stability of the ligand–protein complexes.

Altogether, the results reinforce the promise of Roy and its derivatives as potent anticancer agents and support further experimental validation.