TY - JOUR
T1 - Butenafine and analogues
T2 - An expeditious synthesis and cytotoxicity and antifungal activities
AU - Porras, Ana María Garzón
AU - Terra, Bruna Silva
AU - Braga, Taniris Cafiero
AU - Magalhães, Thais Furtado Ferreira
AU - Martins, Cleide Viviane Buzanello
AU - da Silva, Danielle Letícia
AU - Baltazar, Ludmila Matos
AU - Gouveia, Ludmila Ferreira
AU - de Freitas, Gustavo José Cota
AU - Santos, Daniel Assis
AU - Resende-Stoianoff, Maria Aparecida
AU - Fuchs, Beth Burgwyn
AU - Mylonakis, Eleftherios
AU - de Freitas, Rossimiriam Pereira
AU - de Fátima, Ângelo
N1 - Funding Information:
The authors are thankful for the financial support provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Ângelo de Fátima, Cleide Viviane Buzanello Martins, Daniel de Assis Santos, Maria Aparecida Resende-Stoianoff and Rossimiriam Pereira de Freitas are supported by research fellowships from CNPq. Danielle Leticia da Silva and Thais Furtado Ferreira Magalhães were supported by research fellowships provided by the Brown-Brazil Initiative. Dr. Fuchs and Mylonakis received provisions through a grant from the Brown-Brazil Initiative. The authors thank Esther da Silva Dias for her contribution in the previous project that motivated us to pursue the development of new butenafine analogues as antifungal agents.
Publisher Copyright:
© 2018
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - Antifungal activity
KW - Butenafine
KW - Microwave-assisted synthesis
KW - Multigram-scale synthesis
KW - Schiff base
KW - Trichophyton rubrum
UR - http://www.scopus.com/inward/record.url?scp=85049591062&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049591062&partnerID=8YFLogxK
U2 - 10.1016/j.jare.2018.06.004
DO - 10.1016/j.jare.2018.06.004
M3 - Article
C2 - 30009053
AN - SCOPUS:85049591062
VL - 14
SP - 81
EP - 91
JO - Journal of Advanced Research
JF - Journal of Advanced Research
SN - 2090-1232
ER -