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Candida krusei is one of the most common agents of invasive candidiasis and candidemia worldwide, leading to high morbidity and mortality rates. This species has become a problem due to its intrinsic resistance and reduced susceptibility to azoles and polyenes. Moreover, the number of antifungal drugs available for candidiasis treatment is limited, demonstrating the urgent need for the discovery of novel alternative therapies. In this work, the in vivo and in vitro activities of a new oxadiazole (LMM11) were evaluated against C. krusei. The minimum inhibitory concentration ranged from 32 to 64 μg/mL with a significant reduction in the colony forming unit (CFU) count (~3 log10). LMM11 showed fungicidal effect, similar to amphotericin, reducing the viable cell number (>99.9%) in the time-kill curve. Yeast cells presented morphological alterations and inactive metabolism when treated with LMM11. This compound was also effective in decreasing C. krusei replication inside and outside macrophages. A synergistic effect between fluconazole and LMM11 was observed. In vivo treatment with the new oxadiazole led to a significant reduction in CFU (0.85 log10). Furthermore, histopathological analysis of the treated group exhibited a reduction in the inflammatory area. Taken together, these results indicate that LMM11 is a promising candidate for the development of a new antifungal agent for the treatment of infections caused by resistant Candida species such as C. krusei.
This article was published in the following journal.
Name: PloS one
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Infection with a fungus of the genus CANDIDA. It is usually a superficial infection of the moist areas of the body and is generally caused by CANDIDA ALBICANS. (Dorland, 27th ed)
A seven-membered aromatic ring compound. It is structurally related to a number of naturally occurring antifungal compounds (ANTIFUNGAL AGENTS).
An important nosocomial fungal infection with species of the genus CANDIDA, most frequently CANDIDA ALBICANS. Invasive candidiasis occurs when candidiasis goes beyond a superficial infection and manifests as CANDIDEMIA, deep tissue infection, or disseminated disease with deep organ involvement.
A nitrovinyl furan used as a schistosomicidal agent and proposed for trypanosomiasis, especially Chagas disease.
Antifungal metabolite from several fungi, mainly Trichoderma viride; inhibits protein synthesis by binding to ribosomes; proposed as antifungal and antineoplastic; used as tool in cellular biochemistry.