Chemoenzymatic synthesis of alkaloid derivatives from Amaryllidaceae family by the secretome of Botrytis cinerea and evaluation of antitumoral activity

• Grant number: 25/00709-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 25, 2025
• End date: July 24, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Norberto Peporine Lopes
• Grantee: Winner Duque Rodrigues
• 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: 23/03346-7 - Metabolomic analysis of the chemodiversity present in the Amaryllidaceae family and prospection of anticholinesterase activity, BP.DR

Abstract

The Amaryllidaceae family, is renowned for its abundance of isoquinoline alkaloids, such as galanthamine, lycorine, and tazettine. These compounds exhibit diverse bioactivities, including acetylcholinesterase inhibition, analgesic, anti-inflammatory, antimicrobial, antiviral, and antitumor properties. Among these, galanthamine has been pivotal in the development of drugs for Alzheimer's disease, while others show promise as antitumor agents. Structural modifications of alkaloids have enhanced their antitumor potential and selectivity, addressing challenges such as drug resistance and toxicity. Recent advances in biotransformation technologies offer innovative approaches for diversifying alkaloid structures. Fungal enzyme secretomes, particularly oxidases like laccases, provide chemo-, regio-, and enantioselective transformations, enabling efficient and sustainable modification of bioactive compounds. This study proposes the integration of Amaryllidaceae alkaloids with enzymatic biotransformation strategies to develop novel derivatives with enhanced antitumor potential. By targeting the Wnt signaling pathway, these modified compounds hold promise for addressing TNBC and overcoming tumor resistance. The combination of natural product scaffolds and advanced enzymatic techniques represents a sustainable and innovative strategy for drug discovery, paving the way for new therapeutic agents with significant clinical impact.