title: 2-(benzylideneamino)phenol: a promising hydroxyaldimine with potent activity against dermatophytoses.
abstract: Infections caused by dermatophytes, mainly Trichophyton rubrum,are often vulnerable to relapses upon cessation of antifungal therapy, reinforcing the need of new antifungals. Aldimines have potential biological activities, but there are few reports on their antifungal profile. The aim of this study was to evaluate the antifungal activity of 2-(benzylideneamino)phenol (3A3) and 4-(benzylideneamino)phenol (3A4) against dermatophytes. We determined the minimum inhibitory concentration, minimum fungicidal concentration, time-kill curves and fractional inhibitory concentration of the combination of 3A3, 3A4 and itraconazole against a set of isolates of T. rubrum and T. interdigitale. 3A3 was tested in a murine model of dermatophytoses caused by T. rubrum, and the effect on phagocytosis was assessed. The MIC values ranged from 8 to 32 μg/mL for 3A3 and from 64 to 256 μg/mL for 3A4. The interaction between 3A3 and 3A4 with itraconazole proved to be synergistic and indifferent, respectively. 3A3 was as efficient as itraconazole in reducing the fungal burden on the skin of mice, being this effect associated with the influx of neutrophil and macrophage. Also, 3A3 was able to increase the internalization of conidia by macrophages. Altogether, our data encourage future clinical studies with 3A3 to treat dermatophytoses.
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, Belo Horizonte, Minas Gerais, CEP 31260-901, Brazil.
authors.forename: Alan Kiill
authors.initials: AK
authors.lastname: Gasparto
authors.forename: Ludmila Matos
authors.initials: LM
authors.lastname: Baltazar
authors.forename: Ludmila Ferreira
authors.initials: LF
authors.lastname: Gouveia
authors.forename: Cleiton Moreira
authors.initials: CM
authors.lastname: da Silva
authors.forename: Ricardo Martins Duarte
authors.initials: RM
authors.lastname: Byrro
authors.forename: Milene Alvarenga
authors.initials: MA
authors.lastname: Rachid
authors.forename: Armando da Silva
authors.initials: Ada S
authors.lastname: Cunha Júnior
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: de Resende-Stoianoff
authors.forename: Angelo
authors.initials: A
authors.lastname: de Fátima
authors.forename: Daniel Assis
authors.initials: DA
authors.lastname: Santos
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D019800:Phenol / Q000737:chemistry / Q000494:pharmacology*; D014005:Tinea / Q000188:drug therapy / Q000382:microbiology*; D014249:Trichophyton / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000935:Antifungal Agents; D019800:Phenol