Investigation of Flavonoids Derivatives as PLK-1 Targeted Inhibitor and their Potential Against Lung Tumorigenesis: In-silico Molecular Docking

Background: Lung cancer continues to be the primary cause of cancer-related deaths among both men and women in the United States and globally. Approximately 90% of lung cancer cases are attributable to smoking and the utilization of tobacco products. Nonetheless, additional factors including radon gas, asbestos, air pollution exposure, and chronic infections may contribute to lung carcinogenesis. Recent studies have demonstrated that natural bioactive compounds called polyphenols, derived from plants, possess anticancer properties, effectively eliminating abnormal or malignant cells while preserving normal cells. Flavonoids exhibit antioxidant, antiviral, anticancer, and anti-inflammatory properties. These inexpensive pharmaceutical compounds exhibit considerable biological activities and are advantageous for various chronic conditions, including cancer. Purpose: This study aimed to assess the anti- lung tumorigenesis activity of natural flavonoid through in-silico molecular docking. Method: Polo like kinase 1[PLK 1] was chosen as the target proteins in the current investigation. The bond was found using the Auto Dock software using a grid-based docking method. Compounds' 2D structures were generated, converted to 3D, and subsequently energetically lowered up to an arms gradient of 0.01 using the Merck Molecular Force Field (MMFF). Result: Flavonoids (Fisetin, genistein & naringenin) found to be effective anti-lung cancer component and effectively binds to be target protein PLK-1 with binding energy-7.8, -6.91, -7.17 kcal/mol for fisetin, genistein and naringenin respectively and showed potent inhibitory action on PKL 1. Conclusion: The results of the current investigation demonstrated that the chosen lead molecules (fisetin, genistein, and naringenin) had significant inhibitory effects on the target PLK-1 enzyme, consequently disrupting mitosis and genomic integrity in cancer cells. The molecular docking analysis demonstrated significant binding energy.