Identification of novel molecular targets of plant-derived flavonoid Kaempferol with potential for its antineoplastic actions

Kaempferol (KMF) is a yellow flavonoid compound derived from various green leafy vegetables. Emerging research indicates that KMF exhibits significant antineoplastic activity against a broad spectrum of cancer cell types. However, the specific molecular mechanisms by which KMF exerts tumoricidal ability are not fully understood. This study aims to elucidate these mechanisms by examining the molecular interactions of KMF with a range of critical targets involved in oncogenesis by using in silico approaches/tools. Out of 38 targets selected for investigation, comprehensive docking studies, molecular dynamics simulations, and trajectory analyses revealed that KMF exhibits a strong binding affinity with crucial tumorgenic regulators, including 6-phosphogluconate dehydrogenase (6PGD), Transketolase (TKT), Phosphoglycerate dehydrogenase (PHGDH), Tryptophan 2,3-Dioxygenase (TDO2), Carbonic Anhydrase XII (CA XII), Fatty Acid Synthase (FAS), Liver X Receptor Beta (LXRβ), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and Methionine Aminopeptidase-2 (Met AP2), which play a critical role in oncogenesis. The findings of this study provide valuable insights into the molecular characteristics of KMF's interaction with these regulators, encompassing aspects such as binding stability, interacting amino acids, hydrogen bonds, Van der Waals forces, and various ionic and non-ionic interactions to identify their cancer therapeutic potential. Additionally, we assessed the drug-like properties of KMF using the Lipinski filter and SwissADME, both of which indicate that KMF satisfies the necessary criteria for drug-likeness. In conclusion, the results from the docking and molecular dynamics studies highlight that KMF might hold great potential to be considered as a promising anticancer candidate.