Screening and Antifungal Activity of a β-Carboline Derivative against Cryptococcus neoformans and C. gattii

Cruz, Kátia Santana; Lima, Émerson Silva; Silva, Márcia de Jesus Amazonas da; Souza, Érica Simplício de; Montoia, Andreia; Pohlit, Adrian Martin; Souza, João Vicente Braga de

doi:10.1155/2019/7157845

Cited by 13 publications

(4 citation statements)

References 24 publications

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“…The present study demonstrated fungicidal activity of liriodenine on fungi of the C. neoformans and C. gattii species complexes, showing MIC values ranging from 3.9 to 62.5 µg.mL -1 . Such results are similar to those obtained by Cruz et al [ 33 ], who observed the activity of the synthetic 8-nitrohormone on eight strains of fungi from the Cryptococcus genus, with MICs of 40 µg.mL -1 ; however, the authors did not evaluate whether the compound presented a fungistatic or fungicidal effect.…”

Section: Discussionsupporting

confidence: 89%

Antifungal activity of liriodenine on clinical strains of Cryptococcus neoformans and Cryptococcus gattii species complexes

Levorato-Vinche

Melhem

Bonfietti

et al. 2022

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Cryptoccocal meningitis continues to present high incidence among AIDS patients. The treatment of choice is the synergistic combination of flucytosine (5-FC) with amphotericin B deoxycholate (AmBd) or its lipid formulations. However, 5-FC is unavailable in many countries and AmB demands hospitalization. The combination of AmB with the fungistatic fluconazole (FLC) or the use of high FLC daily doses alone became the choice. Nonetheless, sterilization of cerebrospinal fluid is delayed with FLC monotherapy, mainly with high fungal burden. These findings suggest the search for new antifungal compounds, such as liriodenine. Methods: Liriodenine antifungal activity was evaluated by three procedures: determining the minimum inhibitory concentration (MIC) on 30 strains of the Cryptococcus neoformans ( C. neoformans ) complex and 30 of the Cryptococcus gattii ( C. gattii ) complex, using EUCAST methodology and amphotericin B deoxycholate as control; performing the time-kill methodology in two strains of the C. neoformans complex and one of the C. gattii complex; and injury to cryptococcal cells, evaluated by transmission electron microscopy (TEM). Liriodenine absorption and safety at 0.75 and 1.50 mg.kg -1 doses were evaluated in BALB/c mice. Results: Liriodenine MICs ranged from 3.9 to 62.5 μg.mL -1 for both species complexes, with no differences between them. Time-kill methodology confirmed its concentration-dependent fungicidal effect, killing all the strains below the limit of detection (33 CFU.mL -1 ) at the highest liriodenine concentration (32-fold MIC), with predominant activity during the first 48 hours. Liriodenine induced severe Cryptococcus alterations - cytoplasm with intense rarefaction and/or degradation, injury of organelles, and presence of vacuoles. Liriodenine was better absorbed at lower doses, with no histopathological alterations on the digestive tract. Conclusion: The fungicidal activity confirmed by time-kill methodology, the intense Cryptococcus injury observed by TEM, the absorption after gavage administration, and the safety at the tested doses indicate that the liriodenine molecule is a promising drug lead for development of anticryptococcal agents.

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Section: Discussionsupporting

confidence: 89%

Antifungal activity of liriodenine on clinical strains of Cryptococcus neoformans and Cryptococcus gattii species complexes

Levorato-Vinche

Melhem

Bonfietti

et al. 2022

J. Venom. Anim. Toxins incl. Trop. Dis

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“…The cytotoxicity of the colorants was evaluated in front of MRC‐5 cells (human fibroblast) [25] grown in DMEM medium (Dulbecco's Modified Eagle's Medium), which was supplemented with 10% fetal bovine serum and kept in a CO 2 incubator at 37°C and an atmosphere containing 5% CO 2 . Cells were seeded in 96‐well plates (0.5 × 10 4 cells per well).…”

Section: Methodsmentioning

confidence: 99%

Exploring colorant production by amazonian filamentous fungi: Stability and applications

Oliveira,

Sanches,

Segundo

et al. 2023

J Basic Microbiol

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The aim of this study was to investigate the production, stability and applicability of colorants produced by filamentous fungi isolated from soil samples from the Amazon. Initially, the isolates were evaluated in a screening for the production of colorants. The influences of cultivation and nutritional conditions on the production of colorants by fungal isolates were investigated. The colorants produced by selected fungal isolates were chemically characterized using the Liquid Chromatography‐Mass Spectrometry technique. The antimicrobial and cytotoxic activities, stability evaluation and applicability of the colorants were investigated. As results, we observed that the isolates Penicillium sclerotiorum P3SO224, Clonostachys rosea P2SO329 and Penicillium gravinicasei P3SO332 stood out since they produced the most intense colorants. Compounds produced by Penicillium sclerotiorum P3SO224 and Clonostachys rosea P2SO329 were identified as sclerotiorin and penicillic acid. The colorant fraction (EtOAc) produced by these species has antimicrobial activity, stability at temperature and at different pHs, stability when exposure to light and UV, and when exposed to different concentrations of salts, as well as being nontoxic and having the ability to dye fabrics and be used as a pigment in creams and soap. Considering the results found in this study, it was concluded that fungi from the soil in the Amazon have the potential to produce colorants with applications in the textile and pharmaceutical industries.

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“…Derivative with increased activity Reference properties whose derivatives have been extensively studied in recent years for their anticryptococcal activity [105][106][107][108][109][110] . Recently, derivatives of sampagin, an alkaloid extracted from the stem bark of Cananga odorata Lamarck, have been shown to mediate potent antifungal activity against C. neoformans and gattii species 110 .…”

Section: Starting Materials (Prototype)mentioning

confidence: 99%

Searching for new antifungals for the treatment of cryptococcosis

Sousa

Almeida

Frickmann

et al. 2023

Rev. Soc. Bras. Med. Trop.

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There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available.In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

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Screening and Antifungal Activity of a β-Carboline Derivative against Cryptococcus neoformans and C. gattii

Cited by 13 publications

References 24 publications

Antifungal activity of liriodenine on clinical strains of Cryptococcus neoformans and Cryptococcus gattii species complexes

Antifungal activity of liriodenine on clinical strains of Cryptococcus neoformans and Cryptococcus gattii species complexes

Exploring colorant production by amazonian filamentous fungi: Stability and applications

Searching for new antifungals for the treatment of cryptococcosis

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