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Co-cultivation and Medium Optimization: A Strategy for Discovering Fungal-derived Protease Inhibitors

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Author(s):
Mazucato, Vitor de Souza ; Tonani, Ludmilla ; von Zeska Kress, Marcia Regina ; Andricopulo, Adriano Defini ; Barbosa, Gisele ; Krogh, Renata ; Gomes Ferreira, Leonardo Luiz ; Vieira, Paulo Cezar
Total Authors: 8
Document type: Journal article
Source: CHEMISTRY & BIODIVERSITY; v. N/A, p. 10-pg., 2025-09-02.
Abstract

The fungi Fusarium guttiforme and Phytophthora palmivora were cultivated in four different media (Potato Dextrose Agar, Czapek, rice, and ISP2) and co-cultured to stimulate fungal interactions and enhance secondary metabolite production. Promising extracts were fractionated, yielding compounds such as the iron complex of fusaric acid (1), magnesium complex of fusaric acid (2), haematocin (4), fusarinolic acid (7), and cyclonerodiol (8). These compounds exhibited significant papain inhibitory activity, with compounds 2 and 4 showing IC50 values below 20 mu M. Notable anti-Trypanosoma cruzi activity was also observed, particularly for compounds 2 (50% inhibitory concentration [IC50] = 12.19 mu M) and 4 (IC50 = 13.32 mu M). Additionally, antifungal activity against Candida spp. was detected, with compound 2 and the magnesium complex of 9,10-dehydrofusaric acid complex (3) showing MICs of 50 mu g/mL. This study highlights the potential of fungal co-cultivation and variation in culture medium as effective strategies for discovering novel bioactive protease inhibitors and antiparasitic agents. (AU)

FAPESP's process: 18/14268-9 - Converting natural product leads into structure- and ligand-based drug discovery campaigns against Leishmaniasis and Chagas' Disease
Grantee:Adriano Defini Andricopulo
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 23/15953-5 - Development of pre-clinical candidates for the treatment of Chagas Disease within the scope of the MINDI consortium
Grantee:Gisele Barbosa
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 23/12463-7 - Study of the resistance of Fusarium and Aspergillus clinical isolates to azole antifungals and the biosynthesis of metallic nanoparticles as an antifungal therapeutic alternative.
Grantee:Marcia Regina von Zeska Kress
Support Opportunities: Regular Research Grants
FAPESP's process: 15/50655-9 - FAPESP/MMV/DNDi/UNICAMP/USP Consortium to discover new drugs for the treatment of tropical parasitic diseases
Grantee:Luiz Carlos Dias
Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE