Phytochemical Characterization of Pterocephalus frutescens with In-Silico Evaluation as Chemotherapeutic Medicine and Oral Pharmacokinetics Prediction Study

• Published in: Scientia pharmaceutica 2023-01, Vol.91 (1), p.7
• Main Authors: El-Hela, Atef A., Bakr, Marwa S. Abu, Hegazy, Mostafa M., Dahab, Mohammed A., Elmaaty, Ayman Abo, Ibrahim, Adel Ehab, El Deeb, Sami, Abbass, Hatem S.
• Format: Article
• Language: English
• Subjects: Biosynthesis; Cancer therapies; chemical profiling; Chemotherapy; drug likeness; Enzymes; Estrogens; Fatty acids; Flavonoids; Lipinski’s rule; molecular docking; NMR; Nuclear magnetic resonance; Pharmacokinetics; Phytochemicals; Proteins; pterocephalus frutescens; Tumors
• ISSN: 2218-0532; 0036-8709; 2218-0532
• DOI: 10.3390/scipharm91010007

Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in the field of in-silico modelling and computer-based drug design by orienting and scoring ligands in the active binding site of a target protein. The phytochemical investigation of the Pterocephalus frutescens extract in n-butanol resulted in the isolation and structure elucidation of three iridoids and four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) and Orientin (7), respectively. Molecular docking studies were used to compare the binding energies of the isolated phytochemicals at four biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty acid synthase, and topoisomerase II-DNA complex. The docking study concluded that the isolated compounds have promising cytotoxic activities, in particular, Luteolin-7-O-glucoside (5) and Orientin (7) which exhibited high binding affinities among the isolated compounds at the active sites of the target enzymes; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), respectively, surpassing the corresponding binding scores of the co-crystallized ligands and the reference drugs at these target enzymes. Additionally, among the isolated compounds, Luteolin-7-O-glucoside (5) showed the most outstanding binding affinities at the active sites of the target enzymes; Fatty acid synthase, and Topisomerase II-DNA complex with binding scores of −6.82, and −7.99 Kcal/mol, respectively. Finally, the SwissADME online web tool predicted that most of these compounds possessed acceptable oral bioavailability and drug likeness characteristics.