In silico and in vitro analysis: Unveiling the therapeutic potential of flavonoids against KLF7 in ovarian cancer
Ovarian cancer (OC) remains a major clinical challenge due to late-stage diagnosis, molecular heterogeneity, and the frequent development of chemoresistance, leading to poor patient outcomes. These challenges underscore the urgent need to identify transcriptional regulators that drive tumor progression and may serve as potential therapeutic targets. Krüppel-like factors (KLFs) are a family of transcription factors involved in regulating cellular proliferation, differentiation, apoptosis, and epithelial-mesenchymal transition (EMT). Among them, Krüppel-like factor 7 (KLF7) has been implicated as a tumor-promoting regulator in multiple malignancies, including OC. A full-length structural model of KLF7 obtained from the AlphaFold Protein Structure Database was used for structure-based analyses. Molecular docking and virtual screening were conducted to identify flavonoid compounds with high predicted binding affinity toward KLF7. ADMET analysis was performed to evaluate drug-likeness of compounds. The top-ranked compounds were further analyzed using molecular dynamics (MD) simulations and MM/GBSA calculations to assess complex stability and binding energetics. In vitro study of the most stable flavonoid with OC cell lines was performed to check the inhibitory efficacy. Hesperidin, and diosmin showed stable interactions with KLF7 and favorable binding energies during MD simulations. In vitro experiments demonstrated dose-dependent effects of hesperidin and diosmin on OC cells, indicating potential antiproliferative activity. These findings suggest that hesperidin and diosmin may interact with structurally relevant regions of KLF7 and could serve as potential lead compounds for further investigation.