EXPLORING NATURAL COMPOUNDS TARGETING THE HIPPO PATHWAY FOR POTENTIAL TREATMENT OF MENINGIOMA

Abstract

Drug development which is a bit challenging and complex process that involves the development, discovery, design, and assessment of potential therapeutic agents. Meningioma, most common among the brain tumor which are generally asymptomatic in nature is characterized by the NF2 gene loss. The current treatment options such as resection and radiotherapy have limitations, with high rates of relapse or recurrence. The lack of FDA-approved drugs specific to meningioma necessitates the exploration of alternative approaches. Currently combination of FDA approved drug for other cancer were given to patients but the side effects and failure rates were high. To battle meningioma, natural substances are being researched as potential inhibitors of particular pathways, such as the YAP/TEAD complex in the Hippo signaling pathway. YAP/TEAD complex is responsible for uncontrolled cell progression in meningioma , by targeting this complex we can make a drug or treatment of meningioma. In this study, molecular docking was used to undertake in silico work and inhibition approach was used to find naturally occurring molecules with comparable structures that might potentially interact with the target receptor. out of 50 phytochemical,10 were selected on the basis of bioavailability test and lead likeness The white mulberry Morus alba plant's bark flavonoid, sanggenon N, was discovered to be the study's lead substance. Sanggenon N may have lesser negative effects than synthetic medications because the Sanggenon family of chemicals has demonstrated therapeutic potential. Another flavonoid called isostaivan showed the second-highest binding affinity.. Further analysis confirmed that Sanggenon N could act as an inhibitor of the 6UYC protein, which is the TEAD complex in Homo sapiens, thereby inhibiting the YAP/TEAD complex. This inhibition can potentially suppress cell proliferation and tumor growth in meningioma. It is crucial to emphasize that these results are based on in silico work and that additional validation through wet lab research is required.