Chemoenzymatic Biotransformation and Semisynthesis-Driven Enhancement of Structure-Activity in polyprenylated Benzophenones from Brazilian Red Propolis

• Grant number: 25/13628-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 12, 2026
• End date: January 11, 2027
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Jairo Kenupp Bastos
• Grantee: Matheus Hikaru Tanimoto
• Supervisor: Emerson Ferreira Queiroz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Université de Genève, Switzerland
• Associated to the scholarship: 23/15821-1 - Study of the pharmacokinetic profile of red propolis and its prenylated benzophenones in pre-clinical and clinical models., BP.DD

Abstract

Propolis is a complex natural product with significant therapeutic potential, yet its pharmacokinetic profile remains poorly understood due to chemical heterogeneity and matrix complexity. This project aims to investigate thebiotransformation of polyprenylated benzophenones isolated from Brazilian redpropolis through chemoenzymatic approaches, using enzyme pools from thefungal secretome of Botrytis cinerea. The study integrates chromatographicisolation and structural elucidation of key compounds-guttiferoneE/xanthochymol and oblongifolin B-followed by in vitro chemoenzymaticbiotransformations and chemical semisynthesis to potentially generate novelderivatives with improved selectivity and therapeutic potential. Analytical methodsemploying UHPLC-PDA-ELSD-MS/MS and semi-preparative HPLC will bedeveloped and optimized for monitoring and isolating biotransformation products.The metabolic profiles will be clarified through advanced structural techniques,including NMR spectroscopy. In vitro biological activities will be evaluated toassess the pharmacological relevance of the transformed compounds. Thisresearch will provide critical insights into the metabolism and pharmacokineticsof propolis-derived benzophenones, addressing current gaps in natural productdrug development. The project will strengthen analytical and biotransformationexpertise, contributing to the advancement of safer and more effective naturaltherapeutics. (AU)