Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives
Carolina Orlando Vaso,
Fabiana Pandolfi,
Níura Madalena Bila,
Daniela De Vita,
Martina Bortolami,
Maria José Soares Mendes-Giannini,
Valeria Tudino,
Roberta Costi,
Caroline Barcelos Costa-Orlandi,
Ana Marisa Fusco-Almeida,
Luigi Scipione
Affiliations
Carolina Orlando Vaso
School of Pharmaceutical Science, Universidade Estadual Paulista, Araraquara 14800-903, SP, Brazil
Fabiana Pandolfi
Department of Scienze di Base e Applicate per l’Ingegneria, Sapienza University of Rome, Via Castro Laurenziano 7, 00185 Rome, Italy
Níura Madalena Bila
School of Pharmaceutical Science, Universidade Estadual Paulista, Araraquara 14800-903, SP, Brazil
Daniela De Vita
Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Martina Bortolami
Department of Scienze di Base e Applicate per l’Ingegneria, Sapienza University of Rome, Via Castro Laurenziano 7, 00185 Rome, Italy
Maria José Soares Mendes-Giannini
School of Pharmaceutical Science, Universidade Estadual Paulista, Araraquara 14800-903, SP, Brazil
Valeria Tudino
Department of Chimica e Tecnologia del Farmaco, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Roberta Costi
Department of Chemistry and Technology of Drug, Instituto Pasteur, Fondazione Cenci Bolognetti, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Caroline Barcelos Costa-Orlandi
School of Pharmaceutical Science, Universidade Estadual Paulista, Araraquara 14800-903, SP, Brazil
Ana Marisa Fusco-Almeida
School of Pharmaceutical Science, Universidade Estadual Paulista, Araraquara 14800-903, SP, Brazil
Luigi Scipione
Department of Chimica e Tecnologia del Farmaco, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.
