Butenafine and analogues: An expeditious synthesis and cytotoxicity and antifungal activities

• Main Authors: Ana María Garzón Porras, Bruna Silva Terra, Taniris Cafiero Braga, Thais Furtado Ferreira Magalhães, Cleide Viviane Buzanello Martins, Danielle Letícia da Silva, Ludmila Matos Baltazar, Ludmila Ferreira Gouveia, Gustavo José Cota de Freitas, Daniel Assis Santos, Maria Aparecida Resende-Stoianoff, Beth Burgwyn Fuchs, Eleftherios Mylonakis, Rossimiriam Pereira de Freitas, Ângelo de Fátima
• Format: Article
• Language: English
• Published: Elsevier 2018-11-01
• Series: Journal of Advanced Research
• Online Access: http://www.sciencedirect.com/science/article/pii/S209012321830078X

The incidence of fungal infections is considered a serious public health problem worldwide. The limited number of antimycotic drugs available to treat human and animal mycosis, the undesirable side effects and toxicities of the currently available drugs, and the emergence of fungal resistance emphasizes the urgent need for more effective antimycotic medicines. In this paper, we describe a rapid, simple, and efficient synthetic route for preparation of the antifungal agent butenafine on a multigram scale. This novel synthetic route also facilitated the preparation of 17 butenafine analogues using Schiff bases as precursors in three steps or less. All the synthesized compounds were evaluated against the yeast, Cryptococcus neoformans/C. gattii species complexes and the filamentous fungi Trichophyton rubrum and Microsporum gypseum. Amine 4bd, a demethylated analogue of butenafine, and its corresponding hydrochloride salt showed low toxicity in vitro and in vivo while maintaining inhibitory activity against filamentous fungi. Keywords: Antifungal activity, Butenafine, Microwave-assisted synthesis, Multigram-scale synthesis, Schiff base, Trichophyton rubrum