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Citation
Dalla Lana, D.F., Kaminski, T.F.A., Lavorato, S.N., Merkel, S., Zanette, R.A., da Rosa, P.D., Staudt, K.J., de Ara├║jo, B.V., da Costa, B., Quatrin, P.M., Bazana, L.C.G., Ferreira, F.A., Caurio, C.F.B., de Andrade, S.F., Alves, R.J., Fuentefria, A.M. (2021). In vitro pharmacokinetics/pharmacodynamics modeling and efficacy against systemic candidiasis in Drosophila melanogaster of a bisaryloxypropanamine derivative.  Med. Mycol. 59(1): 58--66.
FlyBase ID
FBrf0247569
Publication Type
Research paper
Abstract

The number of deaths due to systemic fungal infections is increasing alarmingly, which is aggravated by the limitations of traditional treatments and multidrug resistance. Therefore, the research and development of new therapeutic options against pathogenic fungi is an urgent need. To evaluate the fungicidal activity of a synthetic compound, 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride (2j), through time-kill studies and pharmacokinetics/pharmacodynamics (PK/PD) modeling. The protective effect of the compound was also evaluated using the Drosophila melanogaster minihost model of candidiasis. Mathematical modeling of time-kill data of compound 2j was performed to obtain PD characteristics. Additionally, Toll-deficient D. melanogaster flies were infected with a Candida albicans strain and treated with 2j. We observed that compound 2j demonstrated a time- and dose-dependent fungicidal effect against Candida spp. and dermatophytes, even at low concentrations, and rapidly achieved kill rates reaching the maximum effect in less than one hour. The efficacy of the compound against systemic candidiasis in D. melanogaster flies was comparable to that achieved by fluconazole. These results support the potential of compound 2j as a systemic antifungal agent candidate and serve as a starting point for further studies involving mammalian animal models.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Med. Mycol.
    Title
    Medical Mycology
    Publication Year
    1998-
    ISBN/ISSN
    1369-3786 1460-2709
    Data From Reference
    Alleles (2)
    Genes (1)
    Human Disease Models (1)