Pentatropis capensis-Derived Phyto-Compounds: In Silico Analysis Targeting of DCAF1/VprBP in Colorectal Cancer and Biochemical Studies.

Pentatropis capensis (L.f.) Bullock (Apocynaceae) is traditionally used to treat various ailments. However, it lacks systematic scientific validation. This study investigated the phytochemical composition and biological activities of methanolic, ethyl acetate, and hexane leaf extracts. Among them, the methanolic extract showed the highest extractive yield as well as the greatest phenolic (16.5 mg GAE/g) and flavonoid (20 mg QE/g) contents. It also exhibited strong antioxidant activity (DPPH IC50 = 14.85 µg/mL; ABTS IC50 = 26.13 µg/mL; TAC OD = 0.18), notable antibacterial efficacy against Staphylococcus aureus (22 ± 0.3 mm; MIC = 24 µg/mL), and significant anti-inflammatory activity (protein denaturation IC50 = 12.81 µg/mL). The methanolic extract also demonstrated the highest cytotoxicity against HT-29 colon cancer cells (IC50 = 65.62 µg/mL). Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) analyses identified key bioactive compounds. Molecular docking revealed strong binding affinities of major constituents, particularly octadecanedioic acid, cyclohexane derivatives, and n-octacosanol, toward the colorectal cancer target DCAF1/VprBP (3WA0). Further validation through a 100 ns molecular dynamics simulation and MM-PBSA analysis confirmed stable binding with minimal RMSD fluctuations. Overall, these findings highlight the therapeutic potential of P. capensis and support its further in vivo evaluation for cancer treatment.