Identification and validation of flavones and their derivatives as therapeutic agents against gliomas: Applications of machine learning and network pharmacology.

• Grant number: 24/21955-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2025
• End date: December 31, 2029
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Lucas Miguel de Carvalho
• Grantee: Nicolly Clemente de Melo
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Flavones are natural compounds widely recognized for their antioxidant, anti-inflammatory, and anticancer properties, exhibiting significant potential in combating aggressive central nervous system (CNS) tumors, such as gliomas, for which therapeutic options remain limited. This project investigates the use of flavones as therapeutic agents for diffuse gliomas in adults (Astrocytoma, Oligodendroglioma, and Glioblastoma), employing network pharmacology and artificial intelligence tools to develop quantitative structure-activity relationship (QSAR) models. Initially, flavones with reported anticancer activity will be identified through a comprehensive literature review to conduct a preliminary screening. To refine the identification of compounds with higher therapeutic potential, structural similarity methods, such as the Tanimoto index, will be employed to locate analogous compounds. Network pharmacology will be applied to map the molecular targets of flavones and their derivatives using database mining, correlating the identified targets with CNS-associated genes. Artificial intelligence tools will be applied as a filter for compound selection and will aid in the development of QSAR models to predict blood-brain barrier (BBB) permeability and CNS absorption. Interactions among these targets will be analyzed to identify hub genes, facilitating the discovery of novel therapeutic mechanisms. Furthermore, molecular docking studies will be conducted to explore the interactions between flavones and their molecular targets. Experimental assays will also be performed to validate the activity of selected compounds in tumor cells, employing various experimental methodologies to evaluate their efficacy. This study has the potential to identify novel therapeutic compounds with high CNS permeability and relevant molecular targets, contributing to the development of innovative therapies for challenging-to-treat tumors, such as gliomas, through the integration of predictive modeling and experimental validation. (AU)