8-Hydroxyquinoline 1,2,3-triazole derivatives with promising and selective antifungal activity.

Autor:	da Silva NM; Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Gentz CB; Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Reginatto P; Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Fernandes THM; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Kaminski TFA; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Lopes W; Departmento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Quatrin PM; Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Vainstein MH; Departmento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Abegg MA; Instituto de Ciências Exatas e Tecnologia, Universidade Federal do Amazonas, Itacoatiara, AM, Brazil., Lopes MS; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Fuentefria AM; Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., de Andrade SF; Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Jazyk:	angličtina
Zdroj:	Medical mycology [Med Mycol] 2021 May 04; Vol. 59 (5), pp. 431-440.
DOI:	10.1093/mmy/myaa061
Abstrakt:	Fungal infections that affect humans and plants have increased significantly in recent decades. However, these pathogens are still neglected when compared to other infectious agents. Due to the high prevalence of these infections, the need for new molecules with antifungal potential is recognized, as pathogenic species are developing resistance to the main drugs available. This work reports the design and synthesis of 1,2,3-triazole derivatives of 8-hydroxyquinoline, as well as the determination of their activities against a panel of fungal species: Candida spp., Trichosporon asahii, Magnusiomyces capitatus, Microsporum spp., Trichophyton spp. and Fusarium spp. The triazoles 5-(4-phenyl-1H-1,2,3-triazol-1-yl)quinolin-8-ol (12) and 5-(4-(cyclohex-1-en-1-yl)-1H-1,2,3-triazol-1-yl)quinolin-8-ol (16) were more promising, presenting minimum inhibitory concentration (MIC) values between 1-16 µg/ml for yeast and 2-4 µg/ml for dermatophytes. However, no relevant anti-Fusarium spp. activity was observed. In the time-kill assays with Microsporum canis, 12 and 16 presented time-dependent fungicide profile at 96 h and 120 h in all evaluated concentrations, respectively. For Candida guilliermondii, 12 was fungicidal at all concentrations at 6 h and 16 exhibited a predominantly fungistatic profile. Both 12 and 16 presented low leukocyte toxicity at 4 µg/ml and the cell viability was close to 100% after the treatment with 12 at all tested concentrations. The sorbitol assay combined with SEM suggest that damages on the fungal cell wall could be involved in the activity of these derivatives. Given the good results obtained with this series, scaffold 4-(cycloalkenyl or phenyl)-5-triazol-8-hydroxyquinoline appears to be a potential pharmacophore for exploration in the development of new antifungal agents. (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
Databáze:	MEDLINE
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