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  • In vitro inhibitory activity of terpenic derivatives against clinical and environmental strains of the Sporothrix schenkii complex.

In vitro inhibitory activity of terpenic derivatives against clinical and environmental strains of the Sporothrix schenkii complex.

Medical mycology (2014-12-30)
Raimunda Sâmia Nogueira Brilhante, Natalya Fechine Silva, Francisca Jakelyne de Farias Marques, Débora de Souza Collares Maia Castelo-Branco, Rita Amanda Chaves de Lima, Angela Donato Maia Malaquias, Erica Pacheco Caetano, Giovanna Riello Barbosa, Zoilo Pires de Camargo, Anderson Messias Rodrigues, André Jalles Monteiro, Tereza de Jesus Pinheiro Gomes Bandeira, Rossana de Aguiar Cordeiro, José Júlio Costa Sidrim, José Luciano Bezerra Moreira, Marcos Fábio Gadelha Rocha
ABSTRACT

Sporotrichosis is a subacute or chronic subcutaneous infection, caused by the fungus Sporothrix schenkii complex, occurring in human and animal tissues. Potassium iodide and itraconazole have been used as effective therapy for first-choice treatment, while amphotericin B may be indicated for disseminated infection. However, the adverse effects of potassium iodide and amphotericin B or the long duration of therapy with itraconazole often weigh against their use, leading to the search for alternatives for the treatment of severe infections. Terpinen-4-ol and farnesol are components of essential oils present in many plant species and have been described to have antifungal activity against microorganisms. In this study, 40 strains of Sporothrix spp. were tested for the susceptibility to terpinen-4-ol and farnesol. Changes in cytoplasmic membrane permeability were also investigated. Terpenes inhibited all Sporothrix strains with MIC values ranging from 87.9 to 1,429.8 μg/ml for terpinen-4-ol and from 0.003 to 0.222 μg/ml for farnesol. The MFC values ranged from 177.8 to 5,722.6 μg/ml and from 0.027 to 0.88 μg/ml, respectively, for terpinen-4-ol and farnesol. Farnesol was the most active compound for the Sporothrix strains. Significant loss of 260 and 280 nm-absorbing material did not occur after treatment with concentrations equivalent to the MIC and sub-MIC of the tested terpenes, when compared to corresponding untreated samples. The failure of terpenes to lyse Sporothrix cells suggests that their primary mechanism of action is not by causing irreversible cell membrane damage. Thus, new studies are needed to better understand the mechanisms involved in the antifungal activity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(−)-Terpinen-4-ol, ≥95.0% (sum of enantiomers, GC)
Supelco
(+)-Terpinen-4-ol, analytical standard
Supelco
(−)-Terpinen-4-ol, analytical standard
Sigma-Aldrich
Itraconazole, ≥98% (HPLC)
Sigma-Aldrich
Farnesol, 95%
Itraconazole, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
Supelco
Farnesol, analytical standard, stabilized, mixture of isomers
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, Vetec, reagent grade, 99%
Terpinen 4-ol, primary reference standard
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Farnesol, mixture of isomers, ≥95%, stabilized, FG
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%