Flavonoids from Clitoria ternatea as Promising Therapeutic Agents against Ovarian Cancer

Background Flavonoid-based natural products have shown promising anti-cancer potential through dual-pathway inhibition. The PI3K/AKT/mTOR signaling pathway is the most frequently altered pathway in ovarian cancer, making it a critical therapeutic target. Methods Extensive computational studies including molecular docking and 200 nanosecond molecular dynamics simulations were conducted to evaluate the binding affinity, interaction stability, and conformational dynamics of the PI3K (5DXT) and mTOR (5GPG) proteins. Following in-silico validation, naringin-coated zinc oxide nanoparticles incorporating Clitoria ternatea flower extract were formulated to enhance bioavailability and therapeutic efficacy. Additionally, cytotoxic evaluation against SKOV3 ovarian cancer cell lines using MTT assay was performed. Results This study investigated the efficacy of major flavonoid components from Clitoria ternatea flowers, specifically quercetin-3-rutinoside and quercetin-3,7-glucoside, as dual PI3K/mTOR inhibitors. Molecular dynamics analysis revealed that quercetin-3-rutinoside and quercetin-3,7-glucoside exhibited stable interactions with critical amino acid residues throughout the simulation period, promising enhanced stability compared with the standard dual inhibitor gedatolisib. Absorption, Distribution, Metabolism, and Excretion (ADME) profiling identified quercetin derivatives as promising lead hits, despite minor violations of Lipinski’s Rule of Five. Cytotoxic evaluation against SKOV3 ovarian cancer cell lines using MTT assay demonstrated the superior performance of naringin-coated nanoparticles (NC1) with an IC₅₀ value of 144 ± 2.43 μg/mL. Conclusion This synergistic approach, combining natural flavonoids with nanotechnology, provides a novel therapeutic strategy for targeting the dysregulated PI3K/mTOR pathway in ovarian cancer. These findings establish Clitoria ternatea flavonoids are superior candidates for the development of enhanced nanoformulations for anti-cancer therapeutics against ovarian cancer.