scholarly journals Exploiting diverse chemical collections to uncover novel antifungals

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Kali Iyer ◽  
Kaddy Camara ◽  
Martin Daniel-Ivad ◽  
Nicole Revie ◽  
Jennifer Lou ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Fatty Acid Synthase ◽  
Pathogenic Fungi ◽  
Candida Auris ◽  
Chemical Genetic ◽  
Boston University ◽  
Compound Libraries ◽  
Mammalian Cell Growth ◽  
Imminent Threat

The rise in drug resistance amongst pathogenic fungi, paired with the limited arsenal of antifungals available is an imminent threat to our medical system. To address this, we screened two distinct compound libraries to identify novel strategies to expand the antifungal armamentarium. The first collection wasthe RIKEN Natural Product Depository (NPDepo), which was screened for antifungal activity against four major human fungal pathogens: Candida albicans, Candida glabrata, Candida auris, and Cryptococcus neoformans. Through a prioritization pipeline, one compound, NPD6433, emerged as having broad-spectrum antifungal activity and minimal mammalian cytotoxicity. Chemical-genetic and biochemical assays demonstrated that NPD6433 inhibits the essential fungal enzyme fatty acid synthase 1 (Fas1). Treatment with NPD6433 inhibited various virulence traits in C. neoformans and C. auris, and rescued mammalian cell growth in a co-culture model with C. auris. The second compound library screened was adiversity-oriented collectionfrom Boston University. This chemical screen was focused on identifying novel molecules that enhance the activity of the widely deployed antifungal, fluconazole, against C. auris. Through this endeavour, we discovered a potent compound that enhanced fluconazole efficacy against C. auris through increasing azole intracellular accumulation. This activity was dependent on expression of the multidrug transporter geneCDR1, suggesting that this compound targets efflux mechanisms. Furthermore, this molecule significantly reduced fungal burden alone and in combination with fluconazole in a murine model of C. auris disseminated infection. Overall, this work identifies novel compounds with bioactivity against fungal pathogens, revealing important biology, and paving the way for the critical development of therapeutic strategies.

scholarly journals A comparative evaluation of Kumaun Himalayan Gymnosperms for their Antifungal potential against plant pathogenic fungi

2018 ◽  
Vol 7 (3) ◽  
pp. 230-241
Author(s):  
Savita Joshi ◽  
◽  
Parikshit Kumar ◽  
Prabha Pant ◽  
SC Sati ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Ethanol Extract ◽  
Pathogenic Fungi ◽  
Total Activity ◽  
Maximum Activity ◽  
Diffusion Method ◽  
Phytochemical Analysis ◽  
Cedrus Deodara ◽  
Araucaria Cunninghamii

Fungicidal activity of 10 ethnobotanically known Kumaun Himalayan gymnospermous plants namely Araucaria cunninghamii, Biota orientalis, Cedrus deodara, Cephalotaxus griffithi, Cryptomeria japonica Cupressus torulosa, Ginkgo biloba, Juniperus communis, Picea smithiana and Pinus wallichiana were tested against six plant disease causing fungal pathogens by agar well-diffusion method. Forty extracts of these gymnospermic leaves in different organic solvents (methanol, ethanol, chloroform and hexane) were studied by performing the 160 sets of experiments. The MIC values of each extract (where % inhibition ≥ 40%) were also determined. All the plant extracts exhibited strong antifungal activity. Results indicated that all leaves extracts of C. griffithi and G. biloba were found most effective among the tested plants extracts. Hexane extract of C. griffithi was showed highest inhibitory activity against C. falcatum (72%; MIC, 7.81µg/ml) and T. indica (70%; MIC, 15.62µg/ml). On the other hand, ethanol extract of G. biloba also showed remarkable activity against P. oryzae (66% with MIC, 7.81g/ml). While P. wallichiana leave extracts were found less active among the studied plants against all the tested fungal strains. The chloroform extracts were found the most effective against all the tested fungi (10% to 60%), followed by ethanol extract (30-50%), methanol extract (20-40%), while in hexane extracts ranged 10-30% only. The extracts of C. griffithi exhibited superior Relative Antifungal Activity (RAA, 20%), followed by G. biloba and A. cunninghamii (RAA, 19 and 12%, respectively). All data were also analyzed for determination of total activity of plant for each studied species of gymnosperm. C. griffithi had maximum activity i.e. 71 % followed by G. biloba (54%) and A. cunninghamii (33%). C. torulosa showed the least total activity and RAA i.e. 8% and 3%, respectively. All the plant species assayed possess definite antifungal properties and suggested for phytochemical analysis to identify the active principles responsible for their antifungal activity

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

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
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.

scholarly journals Volatile Organic Compound from Trichoderma asperelloides TSU1: Impact on Plant Pathogenic Fungi

2021 ◽  
Vol 7 (3) ◽  
pp. 187
Author(s):  
On-Uma Ruangwong ◽  
Prisana Wonglom ◽  
Nakarin Suwannarach ◽  
Jaturong Kumla ◽  
Narit Thaochan ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Solid Phase ◽  
Sclerotium Rolfsii ◽  
Soil Fungus ◽  
Pathogenic Fungi ◽  
Emerging Diseases ◽  
Plant Diseases ◽  
Gas Chromatography Mass Spectrometry ◽  
Volatile Organic

Soil microorganisms are well studied for their beneficial effects on plant growth and their impact on biocontrol agents. The production of volatile antifungal compounds emitted from soil fungi is considered to be an effective ability that can be applied in biofumigants in the control of plant diseases. A soil fungus, Trichoderma asperelloides TSU1, was isolated from flamingo flower cultivated soil and identified on the basis of the morphology and molecular analysis of the internal transcribed spacer (ITS), rpb2, and tef1-α genes. To test T. asperelloides TSU1-produced volatile organic compounds (VOCs) with antifungal activity, the sealed plate method was used. The VOCs of T. asperelloides TSU1 inhibited the mycelial growth of fungal pathogens that were recently reported as emerging diseases in Thailand, namely, Corynespora cassiicola, Fusarium incarnatum, Neopestalotiopsis clavispora, N. cubana, and Sclerotium rolfsii, with a percentage inhibition range of 38.88–68.33%. Solid-phase microextraction (SPME) was applied to trap VOCs from T. asperelloides TSU1 and tentatively identify them through gas chromatography–mass spectrometry (GC/MS). A total of 17 compounds were detected in the VOCs of T. asperelloides TSU1, and the dominant compounds were identified as fluoro(trinitro)methane (18.192% peak area) and 2-phenylethanol (9.803% peak area). Interestingly, the commercial 2-phenyethanol showed antifungal activity against fungal pathogens that were similar to the VOCs of T. asperelloides TSU1 by bioassay. On the basis of our study’s results, T. asperelloides TSU1 isolated from soil displayed antifungal abilities via the production of VOCs responsible for restricting pathogen growth.

scholarly journals High Reserve in δ-Tocopherol of Peganum harmala Seeds Oil and Antifungal Activity of Oil against Ten Plant Pathogenic Fungi

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4569
Author(s):  
Abdelhamid Hajji ◽  
Fethi Bnejdi ◽  
Mourad Saadoun ◽  
Ibtissem Ben Salem ◽  
Imededdine Nehdi ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
High Performance ◽  
Seed Oil ◽  
Pathogenic Fungi ◽  
Fungal Species ◽  
Seed Oils ◽  
Peganum Harmala ◽  
Gas Chromatograph Mass Spectrometry ◽  
High Level

This investigation included the chemical analysis of Peganum harmala (P. harmala) seed oil and its antifungal properties against 10 fungal species. Seed oils of six populations were analyzed using high performance liquid chromatography (HPLC) and gas chromatograph/mass spectrometry (GC-MS). The HPLC analysis indicated that P. harmala seed oil exhibited a very high level of tocopherol contents, with values in the range of 2385.66–2722.68 mg/100 g. The most abundant tocopherol isomer was δ-tocopherol (90.39%), followed by γ-tocopherol (8.08%) and α-tocopherol (1.14%). We discovered for the first time the presence of tocotrenols in P. harmala seed oils of the six populations studied. The GC-MS analyses revealed that linoleic acid was the main fatty acid (65.17%), followed by oleic acid (23.12%), palmitic acid (5.36%) and stearic acid (3.08%). We also studied the antifungal activity of seed oil of the Medenine (MD) population on ten fungal pathogens. The antifungal effects differed among pathogens and depended on oil concentrations. Seed oil of the MD population caused a significant decrease in mycelial growth of all fungi tested, with values ranging 31.50–82.11%, except for Alternaria sp., which showed no inhibition. The antifungal activity against the 10 selected fungi can be explained by the richness in tocols of the extracted oil and make P. harmala a promising crop for biological control. Furthermore, the importance of fatty acids and the wide geographic spread in Tunisia of this species make this crop a potential source of renewable energy.

Synthetic molecular mimics of naturally occurring cyclopentenones exhibit antifungal activity towards pathogenic fungi

Microbiology ◽  
2011 ◽  
Vol 157 (12) ◽  
pp. 3435-3445 ◽  
Author(s):  
Yi Zhou ◽  
Jonathan Behrendt ◽  
Andrew J. Sutherland ◽  
Gareth Griffiths
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agent ◽  
Fungal Pathogens ◽  
Fungal Spores ◽  
Pathogenic Fungi ◽  
Structural Features ◽  
Alternaria Brassicicola ◽  
Composition Analysis ◽  
Membrane Perturbation ◽  
Naturally Occurring

The naturally occurring reactive electrophilic species 12-oxo-phytodienoic acid (12-oxo-PDA) is a potent antifungal agent, whereas the plant growth regulator jasmonic acid, which is synthesized from 12-oxo-PDA, is ineffective. To address what structural features of the molecule endow it with antifungal activity, we synthesized a series of molecular mimics of 12-oxo-PDA varying in the length of the alkyl chain at its C-4 ring position. The octyl analogue (4-octyl cyclopentenone) was the most effective at suppressing spore germination and subsequent mycelial growth of a range of fungal pathogens and was particularly effective against Cladosporium herbarum and Botrytis cinerea, with minimum fungicidal concentrations in the range 100–200 µM. Introduction of a carboxyl group to the end of the chain, mimicking natural fatty acids, markedly reduced antifungal efficacy. Electrolyte leakage, indicative of membrane perturbation, was evident in both C. herbarum and B. cinerea exposed to 4-octyl cyclopentenone. Lipid composition analysis of the fungal spores revealed that those species with a high oil content, namely Fusarium oxysporum and Alternaria brassicicola, were less sensitive to 4-octyl cyclopentenone. The comparable hydrophobicity of 4-octyl cyclopentenone and 12-oxo-PDA accounts for the similar spore suppression activity of these two compounds. The relative ease of synthesis of 4-octyl cyclopentenone makes it an attractive compound for potential use as an antifungal agent.

scholarly journals Antifungal Activity of Semecarpus anacardium Linn. Oil against Four Phytopathogenic Fungi

2019 ◽  
Vol 2 (3) ◽  
pp. 42-44
Author(s):  
Aarti Patil ◽  
Sadat Quazi
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Pathogenic Fungi ◽  
Phytopathogenic Fungi ◽  
Curvularia Lunata ◽  
Semecarpus Anacardium ◽  
Poisoned Food Technique ◽  
Almost All ◽  
In Vitro Antifungal Activity

The present study was undertaken to evaluate in-vitro antifungal activity of Semecarpus anacardium Linn. oil against four fungal pathogens, viz. Curvularia penniseti, Curvularia lunata, Fusarium oxysporum f. sp. ciceris and Helminthosporium maydis using poisoned food technique. The DMSO extract of S.anacardium oil was found to be more or less active against almost all tested pathogenic fungi with a varied spectrum of reduced growth. C.lunata has shown 93.3% inhibition and F.oxysporum and H.maydis have shown 94.4% inhibition and 100% mycelial inhibitions at 15% and 18% concentrations of the extract respectively. Whereas, C.penniseti was found to be quite sensitive that showed 88.9 inhibitions at 10% concentration but it showed 100% inhibition at 18% concentration.  

SOYBEAN AND FLAX SELECTION METHODS

1970 ◽  
pp. 19-23
Author(s):  
V. М. Lukomets ◽  
S. V. Zelentsov
Keyword(s):  
High Resistance ◽  
Fungal Pathogens ◽  
Selection Process ◽  
Pathogenic Fungi ◽  
Cultivated Plants ◽  
Practical Implementation ◽  
Physiological Basis ◽  
Oil Crops ◽  
Soybean Genotypes ◽  
Genetically Determined

To improve the effectiveness of the soybeans and oil flax breeding, research to improve existing and develop new breeding methods are conducting in all-Russia Research institute of Oil Crops (Krasnodar). One of the improved methods for the soybean breeding, based on the use of sources of complexes of compensatory genes, is the CCG technology, which allows to create varieties with an increased yield of a heterotic level transmitted along the progeny for the entire life cycle of the variety. For the purpose of non-transgenic production of new traits, a theory of polyploid recombination of the genome (TPR) was formulated, which models the mechanism of the natural formation of polymorphism in the centers of origin of cultivated plants. On the basis of this theory, a method of breeding (TPR-technology) has been developed, which makes it possible to obtain recombinant reploids of soybeans and oil flax with an extended spectrum of traits. Of these reploids, the soybean lines with increased sucking force of the roots, providing high drought resistance, were distinguished; cold-resistant soybean lines, which stand in the phase of shoots of freezing to minus 5 °С; lines of oil flax with complete resistance to flax sickness of soil and high resistance to Fusarium; winter-hardy flax lines that withstand winter frosts down to minus 20–23 °С and ripen one and a half months earlier than spring sowings. Another original developed method is the ODCS-technology for isolating and selecting soybean genotypes with high resistance to fungal pathogens. The physiological basis of ODCS-technology is the blocking of osmotic nutrition of pathogenic fungi due to genetically determined increased osmotic pressure in the tissues of host plants. The practical implementation of CCG-, TPR- and ODKS-technologies in the selection process, allowed to create a whole series of soybean and oil flax varieties with improved or new traits.

Improved Production of Two Anti-Candida Lipopeptide Homologues Co- Produced by the Wild-Type Bacillus subtilis RLID 12.1 under Optimized Conditions

2020 ◽  
Vol 21 (5) ◽  
pp. 438-450
Author(s):  
Ramya Ramchandran ◽  
Swetha Ramesh ◽  
Anviksha A ◽  
RamLal Thakur ◽  
Arunaloke Chakrabarti ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Pathogenic Fungi ◽  
Fold Increase ◽  
Production Yield ◽  
Yield Enhancement ◽  
Bioactive Metabolites ◽  
Candida Auris ◽  
Media Formulation ◽  
Static Conditions

Background:: Antifungal cyclic lipopeptides, bioactive metabolites produced by many species of the genus Bacillus, are promising alternatives to synthetic fungicides and antibiotics for the biocontrol of human pathogenic fungi. In a previous study, the co- production of five antifungal lipopeptides homologues (designated as AF1, AF2, AF3, AF4 and AF5) by the producer strain Bacillus subtilis RLID 12.1 using unoptimized medium was reported; though the two homologues AF3 and AF5 differed by 14 Da and in fatty acid chain length were found effective in antifungal action, the production/ yield rate of these two lipopeptides determined by High-Performance Liquid Chromatography was less in the unoptimized media. Methods:: In this study, the production/yield enhancement of the two compounds AF3 and AF5 was specifically targeted. Following the statistical optimization (Plackett-Burman and Box-Behnken designs) of media formulation, temperature and growth conditions, the production of AF3 and AF5 was improved by about 25.8- and 7.4-folds, respectively under static conditions. Results:: To boost the production of these two homologous lipopeptides in the optimized media, heat-inactivated Candida albicans cells were used as a supplement resulting in 34- and 14-fold increase of AF3 and AF5, respectively. Four clinical Candida auris isolates had AF3 and AF5 MICs (100 % inhibition) ranging between 4 and 16 μg/ml indicating the lipopeptide’s clinical potential. To determine the in vitro pharmacodynamic potential of AF3 and AF5, time-kill assays were conducted which showed that AF3 (at 4X and 8X concentrations) at 48h exhibited mean log reductions of 2.31 and 3.14 CFU/ml of C. albicans SC 5314, respectively whereas AF5 at 8X concentration showed a mean log reduction of 2.14 CFU/ml. Conclusion:: With the increasing threat of multidrug-resistant yeasts and fungi, these antifungal lipopeptides produced by optimized method promise to aid in the development of novel antifungal that targets disease-causing fungi with improved efficacy.

Homogenate Extraction of Dihydroartemisinin from Artemisia Hedinii and Its Antifungal Activity

2021 ◽  
Author(s):  
Cong You ◽  
Jun Yu ◽  
Guangjiong Qin ◽  
JinPeng Yang ◽  
Chunlei Yang ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Crude Extract ◽  
Spore Germination ◽  
Alternaria Alternata ◽  
Low Cost ◽  
Pathogenic Fungi ◽  
Extraction Yield ◽  
Optimal Conditions ◽  
Extraction Technology ◽  
Homogenate Extraction

Abstract Background Artemisia hedinii is a well-known traditional Chinese medicine. It can be used to extract dihydroartemisinin (DHA). Objective The purpose of this study was to explore the optimal conditions for the homogenate extraction of DHA from A. hedinii and the antifungal activity of DHA. Methods In this study, single factor experiments and response surface method were used to determine the optimal extraction conditions of crude extract and DHA, the method of spore germination was used to study the antifungal activity of DHA to Alternaria alternata. Result The optimal conditions were found as fellow: ratio of liquid to material 22 mL/g; Extraction time 60 s; soaking time 34 min. Under these conditions, extraction yield of DHA was (1.76 ± 0.04%). When the concentration of crude extract were 0.5 and 8 mg/mL, the spore germination inhibition rates of Alternaria alternata were (17.00 ± 2.05%) and (92.56 ± 2.01%), which were 3.34 and 1.15 times that of DHA standard, respectively. Conclusion Homogenate extraction technology is a fast and efficient method to extract DHA from A. hedinii. The crude extract has significant antifungal activity against A. alternata with low cost, which provides a possibility for the use of DHA in the prevention and treatment of plant pathogenic fungi. Highlights The optimum conditions of the extraction of DHA from A. hedinii by homogenate extraction were obtained. DHA has antifungal activity against A. alternata. Compared with pure DHA, the crude extract has stronger antifungal activity against A. alternata.

scholarly journals Biodirected Synthesis of Silver Nanoparticles Using Aqueous Honey Solutions and Evaluation of Their Antifungal Activity against Pathogenic Candida Spp.

2021 ◽  
Vol 22 (14) ◽  
pp. 7715
Author(s):  
Grzegorz Czernel ◽  
Dominika Bloch ◽  
Arkadiusz Matwijczuk ◽  
Jolanta Cieśla ◽  
Monika Kędzierska-Matysek ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Fungal Growth ◽  
Disc Diffusion ◽  
Candida Spp ◽  
Antifungal Effect ◽  
Synthesis Of Nanoparticles ◽  
Honey Solution ◽  
Diffusion Assay

Silver nanoparticles (AgNPs) were synthesized using aqueous honey solutions with a concentration of 2%, 10%, and 20%—AgNPs-H2, AgNPs-H10, and AgNPs-H20. The reaction was conducted at 35 °C and 70 °C. Additionally, nanoparticles obtained with the citrate method (AgNPs-C), while amphotericin B (AmB) and fluconazole were used as controls. The presence and physicochemical properties of AgNPs was affirmed by analyzing the sample with ultraviolet–visible (UV–Vis) and fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The 20% honey solution caused an inhibition of the synthesis of nanoparticles at 35 °C. The antifungal activity of the AgNPs was evaluated using opportunistic human fungal pathogens Candida albicans and Candida parapsilosis. The antifungal effect was determined by the minimum inhibitory concentration (MIC) and disc diffusion assay. The highest activity in the MIC tests was observed in the AgNPs-H2 variant. AgNPs-H10 and AgNPs-H20 showed no activity or even stimulated fungal growth. The results of the Kirby–Bauer disc diffusion susceptibility test for C. parapsilosis strains indicated stronger antifungal activity of AgNPs-H than fluconazole. The study demonstrated that the antifungal activity of AgNPs is closely related to the concentration of honey used for the synthesis thereof.

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