Herbal Multi-Target Strategy Against Ovarian Cancer: In Silico Evaluation of Elephantopus scaber Phytoconstituents Targeting PI3K, BCL-2, and VEGFR-2
DOI:
https://doi.org/10.48048/tis.2026.13057Keywords:
Elephantopus scaber, BCL2, Ovarian cancer, Molecular docking, PI3K, VEGFR-2, In silico, PhytochemicalsAbstract
Ovarian cancer continues to be one of the deadliest gynecologic cancers, mainly due to delayed diagnosis and treatment resistance. For the treatment of ovarian cancer, a multi-target therapeutic approach that targets key signaling pathways, including PI3K-mediated cell survival, BCL-2-regulated apoptosis, and VEGFR-2-driven angiogenesis, is considered promising. Therefore, using an in silico approach targeting VEGFR-2, BCL-2, and PI3K, this work sought to explore the anticancer potential of phytochemical compounds from the Elephantopus scaber L. extract. After identifying bioactive chemicals from E. scaber by LC-HRMS analysis, AutoDock Vina was used to perform molecular docking against VEGFR-2, BCL-2, and PI3K. SwissADME was used to predict drug-likeness and pharmacokinetic properties, and pkCSM was used to investigate toxicity profiles. Several compounds from the E. scaber extract exhibited substantial binding affinities for the selected targets, as determined by molecular docking. Genistin (−10.1 kcal/mol), apigenin-7-O-glucuronide (−9.9 kcal/mol), and luteolin (−9.6 kcal/mol) demonstrated stronger interactions with VEGFR-2 than the reference inhibitor nintedanib (−7.0 kcal/mol). Additionally, apigenin-7-O-glucuronide had a greater affinity for binding BCL-2 (−7.5 kcal/mol) than obatoclax (−6.8 kcal/mol). While slightly weaker than alpelisib (−10.5 kcal/mol), apigenin-7-O-glucuronide (−9.7 kcal/mol), genistin (−9.3 kcal/mol), and scutellarin (−9.2 kcal/mol) showed the most advantageous contacts in PI3K docking. Most selected compounds fulfilled drug-likeness criteria and displayed low predicted toxicity. The findings highlight E. scaber as a promising source of multi-target anticancer phytochemicals, with apigenin-7-O-glucuronide and genistin emerging as the most potent candidates for further experimental validation.
HIGHLIGHTS
- Apigenin-7-O-glucuronide and genistin showed stronger binding affinities than reference inhibitors toward VEGFR-2 and BCL-2
- Key phytoconstituents demonstrated stable interactions with PI3K, supporting their role in inhibiting survival signaling pathways
- Drug-likeness, pharmacokinetic, and toxicity predictions indicated favorable safety and bioavailability profiles for selected compounds.
- scaber can be considered as a promising source of multi-target herbal candidates for ovarian cancer therapy.
GRAPHICAL ABSTRACT
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