Antifungal Activity of Acylhydrazone Derivatives against Sporothrix spp.

ABSTRACT Sporotrichosis is an emerging mycosis caused by members of the genus Sporothrix. The disease affects humans and animals, particularly cats, which play an important role in zoonotic transmission. Feline sporotrichosis treatment options include itraconazole (ITC), potassium iodide, and amphotericin B, drugs usually associated with deleterious adverse reactions and refractoriness in cats, especially when using ITC. Thus, affordable, nontoxic, and clinically effective anti-Sporothrix agents are needed. Recently, acylhydrazones (AH), molecules targeting vesicular transport and cell cycle progression, exhibited a potent antifungal activity against several fungal species and displayed low toxicity compared to the current drugs. In this work, the AH derivatives D13 and SB-AF-1002 were tested against Sporothrix schenckii and Sporothrix brasiliensis. MICs of 0.12 to 1 μg/ml were observed for both species in vitro. D13 and SB-AF-1002 showed an additive effect with itraconazole. Treatment with D13 promoted yeast disruption with the release of intracellular components, as confirmed by transmission electron microscopy of S. brasiliensis exposed to the AH derivatives. AH-treated cells displayed thickening of the cell wall, discontinuity of the cell membrane, and an intense cytoplasmic degeneration. In a murine model of sporotrichosis, treatment with AH derivatives was more efficient than ITC, the drug of choice for sporotrichosis. Our results expand the antifungal broadness of AH derivatives and suggest that these drugs can be exploited to combat sporotrichosis.

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Synthesis and Antifungal Activity of Coumarins Derivatives Against Sporothrix spp.

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180221115508 ◽

2018 ◽

Vol 18 (2) ◽

pp. 164-171 ◽

Cited By ~ 4

Author(s):

Luana da S.M. Forezi ◽

Luana Pereira Borba-Santos ◽

Mariana F.C. Cardoso ◽

Vitor F. Ferreira ◽

Sonia Rozental ◽

...

Keyword(s):

Antifungal Activity ◽

Antifungal Agents ◽

Sporothrix Schenckii ◽

Public Health Problem ◽

Domestic Animals ◽

Coumarin Derivatives ◽

Sporothrix Brasiliensis ◽

Synthetic Routes ◽

Effective Drugs

Sporotrichosis is a serious public health problem in Brazil that affects human patients and domestic animals, mainly cats. Thus, the search for new antifungal agents is required also due to the emergence and to the lack of effective drugs available in the therapeutic arsenal. The aim of this study was to evaluate the in vitro antifungal profile of two synthetic series of coumarin derivatives against Sporothrix schenckii and Sporothrix brasiliensis. The three-components synthetic routes used for the preparation of coumarin derivatives have proved to be quite efficient and compounds 16 and 17 have been prepared in good yields. The inhibitory activity of nineteen synthetic coumarins derivatives 16a-i and 17a-j were evaluated against Sporothrix spp. yeasts and the most potent compounds were 16b and 17i. However, according to concentrations able to inhibit (minimum inhibitory concentrations) and kill (minimum fungicidal concentrations) the cells, 17i was more effective than 16b against Sporothrix spp. Thus, 17i exhibited good antifungal activity against S. brasiliensis and S. schenckii, suggesting that it is an important scaffold for the development of novel antifungal agents.

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In vitro and in vivo antifungal activity of buparvaquone against Sporothrix brasiliensis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00699-21 ◽

2021 ◽

Author(s):

Luana Pereira Borba-Santos ◽

Thayná Lopes Barreto ◽

Taissa Vila ◽

Kung Darh Chi ◽

Fabiana dos Santos Monti ◽

...

Keyword(s):

Antifungal Activity ◽

Mammalian Cells ◽

Plasma Membranes ◽

Galleria Mellonella ◽

Fungal Growth ◽

Sporothrix Brasiliensis ◽

First Choice ◽

Altered Cell

Sporotrichosis has become an important zoonosis in Brazil and Sporothrix brasiliensis is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex®, was evaluated in vitro and in vivo against feline-borne isolates of S. brasiliensis . Buparvaquone inhibited in vitro fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for S. brasiliensis than mammalian cells. Yeasts treated with a subinhibitory concentration of buparvaquone exhibited mitochondrial dysfunction, ROS and neutral lipid accumulation, and impaired plasma membranes. Also, scanning electron microscopy images revealed buparvaquone altered cell wall integrity and induced cell disruption. I n vivo experiments in a Galleria mellonella model revealed that buparvaquone (single dose of 5 mg/kg) is more effective than itraconazole against infections with S. brasiliensis yeasts. Combined, our results indicate that buparvaquone has a great in vitro and in vivo antifungal activity against S. brasiliensis , revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.

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Synthesis and Biological Activity of Novel Zinc-Itraconazole Complexes in Protozoan Parasites and Sporothrix spp.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01980-19 ◽

2020 ◽

Vol 64 (5) ◽

Cited By ~ 1

Author(s):

Jose Aleixo de Azevedo-França ◽

Renato Granado ◽

Sara Teixeira de Macedo Silva ◽

Gabrielle dos Santos-Silva ◽

Sandra Scapin ◽

...

Keyword(s):

Antifungal Activity ◽

Sporothrix Schenckii ◽

Parasitic Diseases ◽

Protozoan Parasites ◽

Content Type ◽

Sporothrix Brasiliensis ◽

Low Concentrations ◽

Elemental Analyses ◽

Zinc Salts ◽

Medical Importance

ABSTRACT The new complexes Zn(ITZ)2Cl2 (1) and Zn(ITZ)2(OH)2 (2) were synthetized by a reaction of itraconazole with their respective zinc salts under reflux. These Zn-ITZ complexes were characterized by elemental analyses, molar conductivity, mass spectrometry, 1H and 13C{1H} nuclear magnetic resonance, and UV-vis and infrared spectroscopies. The antiparasitic and antifungal activity of Zn-ITZ complexes was evaluated against three protozoans of medical importance, namely, Leishmania amazonensis, Trypanosoma cruzi, and Toxoplasma gondii, and two fungi, namely, Sporothrix brasiliensis and Sporothrix schenckii. The Zn-ITZ complexes exhibited a broad spectrum of action, with antiparasitic and antifungal activity in low concentrations. The strategy of combining zinc with ITZ was efficient to enhance ITZ activity since Zn-ITZ-complexes were more active than the azole alone. This study opens perspectives for future applications of these Zn-ITZ complexes in the treatment of parasitic diseases and sporotrichosis.

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Chemical Composition and Antifungal Activity of Essential Oils from Flowers, Leaves, Rhizomes, and Bulbs of the Wild Iraqi Kurdish Plant Iris Persica

Natural Product Communications ◽

10.1177/1934578x1701200334 ◽

2017 ◽

Vol 12 (3) ◽

pp. 1934578X1701200 ◽

Cited By ~ 1

Author(s):

Hawraz Ibrahim M. Amin ◽

Ahmed Anwar Amin ◽

Solveig Tosi ◽

Giorgio Giacomo Mellerio ◽

Faiq H. S. Hussain ◽

...

Keyword(s):

Antifungal Activity ◽

Essential Oils ◽

Antimicrobial Agents ◽

Trichophyton Mentagrophytes ◽

Fungal Species ◽

Volatile Fraction ◽

In Vitro Tests ◽

Microsporum Canis ◽

Main Component

Essential oils obtained by hydrodistillation of different parts of Iris persica L. were investigated for the first time by GC-FID and GC-MS; moreover, their antifungal activities were determined. 34, 32, 27, and 17 compounds were identified in the oils from air-dried flowers, leaves, rhizomes and fresh bulbs, respectively, representing ≥ 98% each oil. The major constituents of the flower essential oil were phenylethanol (24.8%) and furfural (13.8%), which, as the main component, constituted also 39.0% and 22.2% of the leaf and rhizome volatile fractions, respectively. Phenylacetaldehyde (37.1%) was the main constituent of the bulb volatile fraction. In in vitro tests, moderate antifungal activity was detected for the oils against strains of the human pathogenic fungal species Candida albicans, Microsporum canis, and Trichophyton mentagrophytes, the plant-fungal pathogen Pyricularia oryzae, and the fungal food contaminant Aspergillus carbonarius,. The highest activity was exhibited by the essential oils from leaves and flowers, suggesting that they could be considered natural antimicrobial agents.

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In Vitro Activity of a New Oral Triazole, BMS-207147 (ER-30346)

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.2.313 ◽

1998 ◽

Vol 42 (2) ◽

pp. 313-318 ◽

Cited By ~ 74

Author(s):

Joan C. Fung-Tomc ◽

Elizabeth Huczko ◽

Beatrice Minassian ◽

Daniel P. Bonner

Keyword(s):

Filamentous Fungi ◽

Clinical Laboratory ◽

Sporothrix Schenckii ◽

Fungal Species ◽

National Committee ◽

Microsporum Gypseum ◽

Dematiaceous Fungi ◽

Pseudallescheria Boydii ◽

Broth Macrodilution

ABSTRACT The antifungal activity of BMS-207147 (also known as ER-30346) was compared to those of itraconazole and fluconazole against 250 strains of fungi representing 44 fungal species. MICs were determined by using the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth macrodilution method for yeasts, which was modified for filamentous fungi. BMS-207147 was about two- to fourfold more potent than itraconazole and about 40-fold more active than fluconazole against yeasts. With the NCCLS-recommended resistant MIC breakpoints of ≥1 μg/ml for itraconazole and of ≥64 μg/ml for fluconazole against Candida spp., itraconazole and fluconazole were inactive against strains of Candida kruseiand Candida tropicalis. In contrast, all but 9 (allC. tropicalis) of the 116 Candida strains tested had BMS-207147 MICs of <1 μg/ml. The three triazoles were active against about half of the Candida glabrata strains and against all of the Cryptococcus neoformans strains tested. The three triazoles were fungistatic to most yeast species, except for BMS-207147 and itraconazole, which were fungicidal to cryptococci. BMS-207147 and itraconazole were inhibitory to most aspergilli, and against half of the isolates, the activity was cidal. BMS-207147 and itraconazole were active, though not cidal, against most hyaline Hyphomycetes (with the exception ofFusarium spp. and Pseudallescheria boydii), dermatophytes, and the dematiaceous fungi and inactive againstSporothrix schenckii and zygomycetes. Fluconazole, on the other hand, was inactive against most filamentous fungi with the exception of dermatophytes other than Microsporum gypseum. Thus, the spectrum and potency of BMS-207147 indicate that it should be a candidate for clinical development.

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Arsenic Trioxide Negatively Affects Echinococcus granulosus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04340-14 ◽

2015 ◽

Vol 59 (11) ◽

pp. 6946-6951 ◽

Cited By ~ 6

Author(s):

Bo Wang ◽

Yufeng Jiang ◽

Zhuo Wang ◽

Fangfang Li ◽

Guoqiang Xing ◽

...

Keyword(s):

Electron Microscopy ◽

Arsenic Trioxide ◽

Echinococcus Granulosus ◽

Treatment Options ◽

Small Sample ◽

Content Type ◽

Transmission Electron ◽

New Strategy

ABSTRACTSpillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate thein vitroefficacy of arsenic trioxide (ATO) againstEchinococcus granulosusprotoscolices. Protoscolices ofE. granulosuswere incubatedin vitrowith 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, thein vivoefficacy and possible side effects of ATO need to be explored.

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In Vitro Activity of Novel Antifungal Olorofim against Filamentous Fungi and Comparison to Eight Other Antifungal Agents

Journal of Fungi ◽

10.3390/jof7050378 ◽

2021 ◽

Vol 7 (5) ◽

pp. 378

Author(s):

Ourania Georgacopoulos ◽

Natalie S. Nunnally ◽

Eric M. Ransom ◽

Derek Law ◽

Mike Birch ◽

...

Keyword(s):

Antifungal Activity ◽

Amphotericin B ◽

Fungal Infections ◽

Fusarium Species ◽

Geometric Mean ◽

Treatment Options ◽

Antifungal Susceptibility ◽

Dihydroorotate Dehydrogenase ◽

Drug Classes

Olorofim is a novel antifungal drug that belongs to the orotomide drug class which inhibits fungal dihydroorotate dehydrogenase (DHODH), thus halting pyrimidine biosynthesis and ultimately DNA synthesis, cell growth and division. It is being developed at a time when many invasive fungal infections exhibit antifungal resistance or have limited treatment options. The goal of this study was to evaluate the in vitro effectiveness of olorofim against a large collection of recently isolated, clinically relevant American mold isolates. In vitro antifungal activity was determined for 246 azole-susceptible Aspergillus fumigatus isolates, five A. fumigatus with TR34/L98H-mediated resistance, 19 Rhizopus species isolates, 21 Fusarium species isolates, and one isolate each of six other species of molds. Olorofim minimum inhibitory concentrations (MICs) were compared to antifungal susceptibility testing profiles for amphotericin B, anidulafungin, caspofungin, isavuconazole, itraconazole, micafungin, posaconazole, and voriconazole. Olorofim MICs were significantly lower than those of the echinocandin and azole drug classes and amphotericin B. A. fumigatus wild type and resistant isolates shared the same MIC50 = 0.008 μg/mL. In non-Aspergillus susceptible isolates (MIC ≤ 2 μg/mL), the geometric mean (GM) MIC to olorofim was 0.54 μg/mL with a range of 0.015–2 μg/mL. Olorofim had no antifungal activity (MIC ≥ 2 μg/mL) against 10% of the collection (31 in 297), including some isolates from Rhizopus spp. and Fusarium spp. Olorofim showed promising activity against A. fumigatus and other molds regardless of acquired azole resistance.

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In vivo and in vitro efficacy of crocin against Echinococcus multilocularis

Parasites & Vectors ◽

10.1186/s13071-021-04866-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Chuanchuan Liu ◽

Haining Fan ◽

Lu Guan ◽

Ri-li Ge ◽

Lan Ma

Keyword(s):

Echinococcus Multilocularis ◽

Structural Damage ◽

Secondary Infection ◽

Treatment Options ◽

Collagen Deposition ◽

Mammalian Cell Lines ◽

Human Foreskin Fibroblasts ◽

Transmission Electron

Abstract Background Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larvae of Echinococcus multilocularis. However, current chemotherapy treatment options are based on benzimidazoles [albendazole (ABZ) and mebendazole], which have limited efficacy. Therefore, novel drugs are necessary for the treatment of this disease. Methods The anthelmintic effects of crocin were tested on E. multilocularis metacestodes, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFFs) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. The in vivo efficacy of crocin was investigated in mice following secondary infection with E. multilocularis. Furthermore, collagen deposition and degradation in host tissues around the metacestodes were evaluated. Results In vitro, crocin had a median effective concentration of 11.36 μM against cultured E. multilocularis metacestodes, while it reduced germinal cell viability at a median inhibitory concentration of 10.05 μM. Crocin was less toxic to HFFs and RH mammalian cell lines than to metacestodes. Transmission electron microscopy revealed that crocin treatment resulted in structural damage in the germinal layer. In addition, 60.33 ± 3.06% of protoscoleces were killed by treatment with 10 μM crocin for 7 days, indicating that crocin has a parasiticidal effect. In vivo, the metacestode weight was significantly reduced after the administration of crocin at 50 mg/kg and 100 mg/kg (55.1 and 68.1%, respectively). Metacestode pathology showed structural disruption of the germinal and laminated layers after crocin treatment. The crocin- and ABZ-treated groups presented significant increases in the levels of interleukin (IL)-2 and IL-4. Furthermore, crocin inhibited the expression of matrix metalloproteinases (MMPs) (MMP2 and MMP9) and promoted collagen deposition in the metacestode. Conclusions Crocin was demonstrated to exert parasiticidal activity against E. multilocularis in vitro and in vivo, and can be developed as a novel drug for the treatment of AE. Graphical abstract

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Sesquiterpene Lactones from Centaurea achaia, a Greek Endemic Species: Antifungal Activity

Zeitschrift für Naturforschung C ◽

10.1515/znc-2000-7-810 ◽

2000 ◽

Vol 55 (7-8) ◽

pp. 534-539 ◽

Cited By ~ 21

Author(s):

Helen Skaltsa ◽

Diamanto Lazari ◽

Begoña Garcia ◽

José R. Pedro ◽

Marina Sokovic ◽

...

Keyword(s):

Antifungal Activity ◽

Endemic Species ◽

Sesquiterpene Lactones ◽

Fungal Species ◽

Dilution Method ◽

Aerial Parts ◽

In Vitro Antifungal Activity

Abstract The aerial parts of Centaurea achaia afforded, in addition to several known sesquiterpene lactones and sesquiterpene hydroxyesters, a new germacranolide and a new elemanolide. Their structures were determined as the 8 α-O-(4,5-dihydroxy-tigloyloxy) esters of salonitenolide and of 11,13-dihydromelitensin, respectively. The in vitro antifungal activity of most compounds was tested against nine fungal species using the micro-dilution method. All the tested compounds showed strong antifungal activity.

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Effects of essential oils of Rosmarinus officinalis Linn. and Origanum vulgare Linn. from different origins on Sporothrix brasiliensis and Sporothrix schenckii complex

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-4162-8962 ◽

2016 ◽

Vol 68 (4) ◽

pp. 991-999 ◽

Cited By ~ 2

Author(s):

S.B. Waller ◽

I.M. Madrid ◽

M.B. Cleff ◽

R. Santin ◽

R.A. Freitag ◽

...

Keyword(s):

Essential Oils ◽

Chemical Constituents ◽

Sporothrix Schenckii ◽

Antimicrobial Properties ◽

Rosmarinus Officinalis ◽

Origanum Vulgare ◽

Sporothrix Brasiliensis ◽

Commercial Oil

ABSTRACT Rosmarinus officinalis L. (rosemary) and Origanum vulgare L. (oregano) are known to have antimicrobial properties, but studies on sporotrichosis are scarce. This study aimed to evaluate the anti-Sporothrix spp. activity of essential oils from commercial products and oils extracted from aerial parts of these plants and analyze their chemical constituents. S. schenckii complex and S. brasiliensis (n: 25) isolated from humans, cats, dogs, and environmental soil were tested through M27-A3 guidelines of CLSI with modification for phytotherapics. The essential oils of R. officinalis L. were similar for MIC50 and MFC50 ≤2.25mg/mL for extracted oil; and 4.5mg/mL and 9mg/mL, respectively, for commercial oil. Both products showed MIC90 of 18mg/mL and MFC90 of 36mg/mL. In O. vulgare L., the extracted oil had better activity with MIC50 and MFC50 ≤2.25mg/mL, and MIC90 and MFC90 of 4.5mg/mL, whereas the commercial oil showed MIC50 and MFC50 of 9mg/mL and MIC90 18mg/mL, respectively, and MFC90 of 36mg/mL. Through gas chromatography (CG/FID), thymol and α-terpinene were majority for extracted oil of O. vulgare L., and carvacrol and γ-terpinene made up the majority of the commercial oil. Both essential oils of R. officinalis L. showed 1,8-cineole and α-pinene as major. The fungal isolates were susceptible to all tested essential oils, including in itraconazole-resistant S. brasiliensis isolates. The extracted and commercial oils of the plants presented in vitro anti-Sporothrix spp. activity, and they are promising for treatment of sporotrichosis, including in cases refractory to itraconazole. More studies should be performed about toxicity and in vivo efficacy for its safe use.

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