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 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.

A New Prenylisoflavone from Ulex jussiaei

2002 ◽  
Vol 57 (7-8) ◽  
pp. 609-613 ◽  
Author(s):  
Patrícia Máximoa ◽  
Ana Lourenço ◽  
Sónia Savluchinske Feio ◽  
José Carlos Roseiro
Keyword(s):  
Antifungal Activity ◽  
Structural Features ◽  
Cladosporium Cucumerinum ◽  
Naturally Occurring ◽  
Bioautographic Method

A new naturally occurring isoflavone, derrone, was isolated from Ulex jussiaei (Leguminosae) together with the isoflavones ulexins A-C, lupalbigenin, isolupalbigenin, 7-O-methylisolupalbigenin, isoderrone, ulexone A and isochandalone, the pterocarpans (6aR,11aR)-(-)- maackiain, (6aR,11aR)-(-)-2-methoxymaackiain and (6aR,11aR)-(-)-4-methoxymaackiain, the chalcone 4-hydroxylonchocarpine and the dihydrochalcone crotaramosmine. The antifungal activity of the new compound was tested by a bioautographic method against Cladosporium cucumerinum, and as expected from structural features it proved to have no activity.

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 Understanding In-Silico Approaches to Design Synthetic Antifungal Peptides to Combat Fungal Infections like Mucormycosis

2021 ◽  
Vol 8 (6) ◽  
Author(s):  
Bajwa T ◽  
◽  
Sharma R ◽  
Keyword(s):  
In Silico ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Structural Features ◽  
Antifungal Drugs ◽  
Diverse Range ◽  
Naturally Occurring ◽  
Antifungal Peptides ◽  
Range Of Functions

Antimicrobial peptides are the small sized molecule ranging in size from 2 to 9 kDa with expansive range of antimicrobial activity against bacteria, fungi, viruses etc. They are also used as first line of defense against various pathogens. With the emergence of various fungal infections in the present day and uprising antifungal resistance has made the choice of antifungal drugs very limited, the conventional drugs are slowly becoming ineffective to these fungal pathogens. Researchers have turned to these naturally occurring molecules which represent diverse range of functions and structural features but these naturally occurring peptides exhibit high toxicity, instability and low specificity towards the target which can be combatted by using various in silico and computational approaches to design and modify these AMPs in such a way that their efficiency is increased. In this article, we have specifically focused on Mucormycosis infection because of its high mortality rates and a very few synthetic AMPs have been produced against Mucorales considering the severity of this disease and the rapid surge in Mucormycosis cases emerged in the country. In this paper we will discuss about the present scenario of the disease, AMPs as antifungal therapy, role, classification of antifungal peptides, mechanism of action, advantages and limitations of natural AMPs, important physicochemical properties taken into account while designing synthetic AMPs (SAMPs) and the workflow pipeline to characterize and predict potential synthetic AMPs by using the existing web servers, databases and bioinformatics tools to develop new alternatives of conventional drugs available in the market against fungal infections.

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.

Synthesis of 7,3'-Epoxy-8,4'-Oxyneolignane-1’-Carboxylic Acid from Natural Eusiderin A and its Activity Against Trichophyton mentagrophytes

2019 ◽  
Vol 7 (1) ◽  
pp. 44-54
Author(s):  
Muhaimin Muhaimin ◽  
Syamsurizal Syamsurizal ◽  
Madyawati Latief ◽  
Rahmi Iskandar ◽  
Anis Yohana Chaerunisaa ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Carboxylic Acid ◽  
Antifungal Agent ◽  
Primary Alcohol ◽  
Pathogenic Fungi ◽  
Trichophyton Mentagrophytes ◽  
Diffusion Method ◽  
Wacker Oxidation ◽  
Strong Activity

Background: Eusiderin A is a neolignan derivate, which makes up the majority of the secondary metabolite of Eusideroxylon zwageri. It has been reported as a potent biopesticide and antifungal agent. Previous studies on the oxidation of terminal methylene of the allylic chain in Eusiderin A have been able to produce primary alcohol, pinacol, and an aldehyde which demonstrated strong activity against plant pathogenic fungi, therefore activity against dermal fungi needs to be studied. Objective: The current study aims to improve the hydrophilicity of Eusiderin A via oxidation of the allylic chain in order to derive a potent antifungal property. Methods: Transformation of Eusiderin A has been achieved by using the Wacker Oxidation Method in combination with the α-Hydroxylation-Ketone Method to produce 7,3’-epoxy-8,4’-oxyneolignane-1’- carboxylic acid. The structure of the 7,3’-epoxy-8,4’-oxyneolignane-1’-carboxylic acid was identified from spectroscopy data. The in vitro antifungal activity study was performed using the paper disc diffusion method against Trichophyton mentagrophytes. Results: New molecule of natural Eusiderin A through the oxidation of the allylic chain to increase the hydrophilicity of Eusiderin A has been designed. Based on the observed UV, IR, 1H and 13C-NMR, and MS spectra, it can be stated that the 7,3’-epoxy-8,4’-oxyneolignane-1’-carboxylic acid has been formed. At a concentration of 50 ppm, this compound showed antifungal activity against Trichophyton mentagrophytes. Conclusion: It can be concluded that the 7,3’-epoxy-8,4’-oxyneolignane-1’-carboxylic acid is a potent antifungal agent as it is able to inhibit the Trichophyton mentagrophytes colonies growth.

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 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.  

Sign in / Sign up

Export Citation Format

Share Document