Molecular Docking and Pharmacokinetic Profiling of GC-MS-Identified Phytochemicals from Peganum harmala-Derived Essential Oil: In Silico Assessment of Binding Affinity Toward PCOS-Related Targets

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, characterized by hyperandrogenism, insulin resistance, and ovarian dysfunction. Current therapies are often associated with adverse effects, highlighting the need for safer therapeutic alternatives. Peganum harmala (P. harmala), a medicinal plant rich in bioactive metabolites, was investigated through in silico approaches to identify compounds with predicted binding affinity for the androgen receptor (AR), steroid 17α-hydroxylase/17,20-lyase (CYP17A1), and glycogen synthase kinase-3 beta (GSK-3β). GC-MS analysis of P. harmala leaf essential oil collected in Riyadh, Saudi Arabia, identified 109 compounds, with terpenoids as the dominant class (21.89%). The major constituents were cis-chrysanthenyl acetate (3.48%), cis-β-damascenone (3.06%), farnesylacetone (1.44%), β-calacorene (1.36%), dihydroedulan II (1.04%), and trans-calamenene (0.46%). In silico ADMET evaluation indicated that most compounds complied with Lipinski’s rule of five and showed favorable predicted pharmacokinetic properties. Safety profiling suggested an overall acceptable toxicity profile, with minimal predicted CYP450 inhibition, except for L11, which showed broader inhibitory potential. Molecular docking showed that L15 (trans-calamenene), L14 (dihydroedulan II), L6 (β-calacorene), L3 (farnesylacetone), and L8 exhibited higher predicted binding affinity toward the androgen receptor; L3, L10 (cis-β-damascenone), and L16 (cis-chrysanthenyl acetate) interacted with CYP17A1, while L3, L9, and L6 exhibited higher affinity toward GSK-3β. Overall, these findings provide hypothesis-generating in silico predictions of ligand–target binding affinities and drug-likeness profiles. These computational findings highlight the importance of future experimental investigations to substantiate the biological activity, pharmacokinetic behavior, and safety profile of P. harmala constituents.