Biocatalytic Studies of the Furanocoumarins Angelicin and Chalepensin

Bioconversion studies conducted on the furanocoumarins angelicin and chalepensin have revealed that angelicin was metabolized by Lipomyces lipofer (ATCC 10742) to give the corresponding reduced acid 3 and chalepensin was transformed by Cunninghamella blakesleeana (SC-2138) to give the diol metabolite 4. The structures of the new metabolites have been established on the basis of spectral data. The absolute stereochemistry around C-2″ in 4 was confirmed by Horeau's method. Angelicin and chalepensin were shown to possess antifungal activity against Candida albicans and Cryptococcus neoformans.

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Novel Antifungal Compounds Discovered in Medicines for Malaria Venture’s Malaria Box

mSphere ◽

10.1128/msphere.00537-17 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 7

Author(s):

Eric H. Jung ◽

David J. Meyers ◽

Jürgen Bosch ◽

Arturo Casadevall

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Fungal Pathogens ◽

Pathogenic Fungi ◽

Cryptococcus Gattii ◽

Antifungal Drugs ◽

Resistant Bacteria ◽

Animal Cells ◽

Malaria Box

ABSTRACTSimilarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity. Consequently, there is a need for new and more effective antifungal drugs. We have identified compounds with significant antifungal activity in the Malaria Box (Medicines for Malaria Ventures, Geneva, Switzerland) that have higher efficacy than some of the currently used antifungal drugs. Our best candidate, MMV665943 (IUPAC name 4-[6-[[2-(4-aminophenyl)-3H-benzimidazol-5-yl]methyl]-1H-benzimidazol-2-yl]aniline), here referred to as DM262, showed 16- to 32-fold-higher activity than fluconazole againstCryptococcus neoformans. There was also significant antifungal activity in other fungal species with known antifungal resistance, such asLomentospora prolificansandCryptococcus gattii. Antifungal activity was also observed against a common fungus,Candida albicans. These results are important because they offer a potentially new class of antifungal drugs and the repurposing of currently available therapeutics.IMPORTANCEMuch like the recent increase in drug-resistant bacteria, there is a rise in antifungal-resistant strains of pathogenic fungi. There is a need for novel and more potent antifungal therapeutics. Consequently, we investigated a mixed library of drug-like and probe-like compounds with activity inPlasmodiumspp. for activity against two common fungal pathogens,Cryptococcus neoformansandCandida albicans, along with two less common pathogenic species,Lomentospora prolificansandCryptococcus gattii. We uncover a previously uncharacterized drug with higher broad-spectrum antifungal activity than some current treatments. Our findings may eventually lead to a compound added to the arsenal of antifungal therapeutics.

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Antifungal Activity of the Essential Oil of Echinops kebericho Mesfin: An In Vitro Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3101324 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Tamirat Bekele Beressa ◽

Serawit Deyno ◽

Paul E. Alele

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Essential Oil ◽

Cryptococcus Neoformans ◽

Antioxidant Properties ◽

Pathogenic Fungi ◽

Diffusion Method ◽

Potential Candidate ◽

Standard Drug

Background. Echinops kebericho is an endemic medicinal plant in Ethiopia widely used in the treatment of infectious and noninfectious diseases. Essential oils are known for their antibacterial, antifungal, antiviral, insecticidal, and antioxidant properties. This study evaluated the antifungal activity of essential oil from E. kebericho against four common pathogenic fungi and two standard strains. Methods. The essential oil was obtained by hydrodistillation. The antifungal screening was done by agar well diffusion method. Minimal inhibitory concentrations (MICs) were determined by broth microdilution. Minimal fungicidal concentrations (MFCs) were determined by subculturing fungal strains with no visible growth onto a Sabouraud dextrose agar (SDA) plate. Results. Candida albicans and Cryptococcus neoformans were highly sensitive while Aspergillus flavus did not show sensitivity up to 1 mg/ml of essential oil; MICs ranged from 0.083 mg/ml to 0.208 mg/ml. Concentration and fungal species showed significant dose-dependent associations ( p < 0.0001 ) with antifungal activity. The MICs of essential oil were comparable to those of the standard drug (fluconazole) against C. glabrata and C. krusei. The lowest MFC of the essential oil was observed against Candida parapsilosis (0.145 mg/ml) while the highest MFC was against Candida krusei (0.667 mg/ml). Conclusion. Echinops kebericho essential oil showed noteworthy antifungal activity against Cryptococcus neoformans, Candida albicans, and Candida glabrata and could be a potential candidate for further antifungal drug development.

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

International Journal of Microbiology ◽

10.1155/2019/7157845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Kátia Santana Cruz ◽

Emerson Silva Lima ◽

Marcia de Jesus Amazonas da Silva ◽

Erica Simplício de Souza ◽

Andreia Montoia ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Active Compound ◽

Cell Walls ◽

Human Fibroblasts ◽

Lead Compound ◽

Fungal Cell ◽

Fungal Cell Walls

Background. Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and β-carboline alkaloids and derivatives against Cryptococcus neoformans and C. gattii. Methods. MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against C. neoformans and C. gattii genotypes VNI and VGI, respectively. A single active compound was further evaluated against C. neoformans genotypes VNII, VNIII, and VNIV, C. gattii genotypes VGI, VGIII, and VGIV, Candida albicans ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids). Results. Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 μg/mL) of several C. neoformans and C. gattii genotypes. It was not toxic to fibroblasts (IC50 > 50 µg/mL) nor did it alter fungal cell walls or the concentration of ergosterol in C. albicans or C. neoformans. It increased leakage of substances that absorb at 260 nm. Conclusions. The synthetic β-carboline 8-nitroharmane significantly inhibits pathogenic Cryptococcus species and is interesting as a lead compound towards new therapy for Cryptococcus infections.

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Antifungal activity of Swietenia mahogany on Candida albicans and Cryptococcus neoformans

Journal of Microbiology and Antimicrobials ◽

10.5897/jma10.067 ◽

2013 ◽

Vol 5 (6) ◽

pp. 55-59

Author(s):

Shyam Sundar

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Cryptococcus Neoformans

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Antifungal Activity of Plumericin and Isoplumericin

Natural Product Communications ◽

10.1177/1934578x1100601101 ◽

2011 ◽

Vol 6 (11) ◽

pp. 1934578X1100601 ◽

Cited By ~ 1

Author(s):

Dharmendra Singh ◽

Umakant Sharma ◽

Parveen Kumar ◽

Yogesh K Gupta ◽

M. P. Dobhal ◽

...

Keyword(s):

Candida Albicans ◽

Minimum Inhibitory Concentration ◽

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Inhibitory Concentration ◽

Chloroform Extract ◽

Drug Candidate ◽

Minimum Fungicidal Concentration ◽

In Vitro Antifungal Activity

This study evaluated the in vitro antifungal activity of the chloroform extract of Plumeria bicolor and its phytoconstituents plumericin and isoplumericin against Candida species and Cryptococcus neoformans by measuring the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC). Plumericin's consistently high activity against Candida albicans, C. krusei, C. glabrata, C. tropicalis and Cryptococcus neoformans was more potent than isoplumericin and the standard antifungal drug nystatin suggesting its potential as a drug candidate for candidiasis and cryptococcosis.

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In vitro Antifungal Activity of Dihydropyrimidinones/Thiones Against Candida albicans and Cryptococcus neoformans

Current Bioactive Compounds ◽

10.2174/1573407214666180926115745 ◽

2020 ◽

Vol 15 (6) ◽

pp. 648-655

Author(s):

Gabriel O. de Azambuja ◽

Laura Svetaz ◽

Itamar L. Gonçalves ◽

Patricia F. Corbelini ◽

Gilsane L. von Poser ◽

...

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Drug Design ◽

Cryptococcus Neoformans ◽

Biginelli Reaction ◽

Fungal Growth ◽

Chemical Library ◽

Antifungal Effect ◽

In Vitro Antifungal Activity

Background: Since the Monastrol discovery in 1999 as the first inhibitor of Eg5, functionalized dihydropyrimidinones/thiones (DHPMs) have emerged as prototypes for drug design in different targets. The present work aimed to evaluate the antifungal activity of a chemical library of DHPMs. Methods: The compounds were obtained employing Biginelli reaction. Their antifungal activities were assessed against C. neoformans and C. albicans. Results: The compounds 1-i and 1-k inhibited moderately the fungal growth of C. neoformans, with compound 2-k presenting MIC80 values of 62.5-125 µg·mL-1. Considering activity against C. albicans, the compounds 1-i and 1-n present an MIC50 value of 125-250 µg·mL-1. Conclusion: The changes performed in DHPM scaffold appear to be valuable for generating compounds with potential antifungal effect.

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Regioisomers of Acylcoumarins from the Flowers of Mammea siamensis

Natural Product Communications ◽

10.1177/1934578x0700200509 ◽

2007 ◽

Vol 2 (5) ◽

pp. 1934578X0700200 ◽

Cited By ~ 2

Author(s):

Chulabhorn Mahidol ◽

Hunsa Prawat ◽

Wirongrong Kaweetripob ◽

Somsak Ruchirawat

Keyword(s):

Spectral Data ◽

Hexane Extract ◽

The Absolute ◽

New Compounds ◽

Modified Mosher’S Method ◽

Absolute Stereochemistry

Chemical exploration of the n-hexane extract of the flowers of Mammea siamensis led to the identification of six new compounds, deacetylmammea E/AC cyclo D (1), deacetylmammea E/AA cyclo D (2), deacetylmammea E/AB cyclo D (3), deacetylmammea E/BC cyclo D (4), deacetylmammea E/BB cyclo D (5), and deacetylmammea E/BA cyclo D (6). The structures of these compounds were elucidated by analysis of the spectral data. The absolute stereochemistry of 1, 5 and 6 were established by the modified Mosher's method.

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Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus Induces an Antifungal Activity in Mouse Serum, which is Different from Transferrin

Journal of Veterinary Medical Science ◽

10.1292/jvms.001459 ◽

2009 ◽

Vol 71 (11) ◽

pp. 1459-1464

Author(s):

Ken-ichi OKAZAKI ◽

Masahiro ASAKURA ◽

Norihiko SUGIMOTO ◽

Atsushi HINENOYA ◽

Shinji YAMASAKI

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Aspergillus Fumigatus ◽

Cryptococcus Neoformans ◽

Mouse Serum

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In vitro antifungal activity of eugenol and vanillin against Candida albicans and Cryptococcus neoformans

Canadian Journal of Microbiology ◽

10.1139/m82-184 ◽

1982 ◽

Vol 28 (11) ◽

pp. 1235-1241 ◽

Cited By ~ 57

Author(s):

Chuenchit Boonchird ◽

T. W. Flegel

Keyword(s):

Candida Albicans ◽

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Tube Formation ◽

Toxicity Tests ◽

Short Term ◽

Minimal Inhibitory Concentrations ◽

The Mean ◽

In Vitro Antifungal Activity

Eugenol and vanillin were examined for in vitro antifungal activity against the medically important yeasts, Candida albicans and Cryptococcus neoformans. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) were determined for each compound against 31 strains of C. albicans and 33 strains of C. neoformans. With eugenol, the mean MIC's for C. albicans and C. neoformans were 625 and 293 μg/mL, respectively, while the mean MFC's were 1209 and 521 μg/mL, respectively. With vanillin, the mean MIC's for C. albicans and C. neoformans were 1250 and 738 μg/mL, respectively, while the mean MFC's were 5000 and 1761 μg/mL, respectively. With C. albicans, inhibition and retardation of growth were similar for yeast and mycelial forms, but germ tube formation was inhibited at concentrations lower than those which inhibited growth. Short-term toxicity tests with mice using the intraperitoneal route gave maximum tolerated doses of 62.5 mg/kg for eugenol and 125 mg/kg for vanillin and excluded their use as therapeutic agents for systemic mycoses.

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