Isolation, Molecular Docking, and ADME Prediction of Bioactive Phytochemicals from Pterocephalus frutescens Targeting Cancer-Related Enzymes

In-silico modeling and computer-aided drug design benefit from the virtual evaluation of promising lead chemotherapeutic phytochemicals sourced from medicinal plants, which is accomplished by orienting and scoring ligands within a target protein's active binding cavity. The phytochemical exploration of a Pterocephalus frutescens n-butanol extract afforded the isolation and structural determination of three iridoids alongside four flavonoids, established respectively as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5), Isoorientin (6), and Orientin (7). The binding energies of these isolated phytochemicals were compared via molecular docking across four cancer-relevant biological receptors: aromatase, carbonic anhydrase IX, fatty acid synthase, and the topoisomerase II-DNA complex. Findings from the docking work revealed that the purified compounds harbor encouraging cytotoxic capabilities, especially Luteolin-7-O-glucoside (5) and Orientin (7), which registered remarkable binding affinities within the panel of isolates at the active pockets of the target proteins; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), correspondingly, outperforming the documented binding scores of both co-crystallized ligands and standard drugs at these enzymatic targets. Additionally, within the set of separated constituents, Luteolin-7-O-glucoside (5) exhibited the strongest binding interactions at the active sites of Fatty acid synthase and the Topoisomerase II-DNA complex, yielding binding values of −6.82 and −7.99 Kcal/mol, respectively. In the end, predictions from the SwissADME online portal indicated that most of these phytomolecules have satisfactory oral bioavailability and drug-likeness.