Unveiling the Bioactive Potential of <i>Allium colchicifolium</i> Boiss Bulb Flavonoids: Anti-cancer Activities, and Computational Exploration of Anti-angiogenic Mechanisms

Abstract

Background: Plants of the genus Allium show significant anti-cancer properties due to various phytochemicals, including flavonoids. Objectives: This study investigated the cytotoxic activities of the methanolic extract of Allium colchicifolium bulbs and its purified flavonoids. It also assessed the anti-angiogenic activities, a key mechanism of anti-cancer agents. Methods: The methanolic extract was fractionated using column chromatography (CC) on silica gel RP-18 and polyamide SC-6, then purified with Sephadex LH-20. The compounds were identified through spectroscopic methods such as nuclear magnetic resonance (NMR) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Cytotoxicity and anti-angiogenic activities were evaluated using the MTT assay and the chick chorioallantoic membrane (CAM) assay, respectively. Computational modeling explored the potential anti-angiogenic mechanisms of the purified compounds. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling predicted drug-likeness features. Results: Three flavonoids — quercetin 3-O-rutinoside (1), isorhamnetin 3-O-glucoside (2), and quercetin (3) — were isolated and identified. Compounds 2 and 3 showed the highest cytotoxicity against PC3 (prostate cancer, IC50 = 1.72 ± 0.11 µg/mL) and MCF-7 (breast cancer, IC50 = 1.64 ± 0.11 µg/mL) cell lines. The methanolic extract and compound 3 also had potent anti-angiogenic effects with IC50 values of 4.2 ± 0.25 and 5.3 ± 0.3 µg/mL, respectively. Molecular docking indicated that compounds 1 and 3 had the strongest interactions with the vascular endothelial growth factor receptor (VEGFR)-1, consistent with their anti-angiogenic activity. The ADMET profiling showed that compound 3 had the highest similarity to drug-like molecules. Conclusions: This was the first phytochemical study of flavonoids in A. colchicifolium bulbs. The results suggest that these bulbs could serve as a natural source for cancer prevention and treatment, owing to their cytotoxic and anti-angiogenic properties. Further research is needed to confirm these findings, and in vivo studies are essential to validate their therapeutic potential.