Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives

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Vaso, Carolina Orlando ; Pandolfi, Fabiana ; Bila, Niura Madalena ; De Vita, Daniela ; Bortolami, Martina ; Soares Mendes-Giannini, Maria Jose ; Tudino, Valeria ; Costi, Roberta ; Costa-Orlandi, Caroline Barcelos ; Fusco-Almeida, Ana Marisa ; Scipione, Luigi

• Document type: Journal article
• Source: PHARMACEUTICS; v. 14, n. 3, p. 19-pg., 2022-03-01.

Abstract

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 mu g/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 mu g/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 mu g/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. (AU)

• FAPESP's process: 20/15586-4 - Establishment of a three-dimensional model to determine the pharmacological efficacy and safety of nitrofuran and indoles derivatives and evaluation of Histoplasma capsulatum infection
• Grantee: Carolina Orlando Vaso
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/11836-0 - SELECTION OF THERAPEUTIC TARGETS AND/OR BIOMARKERS FROM GLOBAL RESPONSE TRANSCRIPTIONAL OF ALVEOLAR MACROPHAGES INFECTED BY H. capsulatum BIOFILMS
• Grantee: Ana Marisa Fusco Almeida
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/22188-8 - Evaluation of the interaction of biofilms mono and dual-species of Candida spp and dermatophytes photodynamic therapy combined with 2-chalcone
• Grantee: Níura Madalena Bila
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/18388-6 - Role of biofilm in the pathogenesis of dermatophytosis and development of combat strategies
• Grantee: Caroline Barcelos Costa Orlandi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral