Antifungal activity of rare actinobacterium isolated from forest soil

2021 ◽  
Vol 16 (10) ◽  
pp. 92-101
Author(s):  
Muralidharan Sasidhar ◽  
Selvam Masilamani ◽  
Abirami Baskaran ◽  
Manigundan Kaari ◽  
Radhakrishnan Manikkam
Keyword(s):  
Antifungal Activity ◽  
Forest Soil ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Carbon Sources ◽  
Nitrogen Sources ◽  
Antifungal Drugs ◽  
Antifungal Compound ◽  
Antifungal Compounds ◽  
Promising Source

Prolonged use of antifungal drugs has led to the emergence of drug resistant fungal pathogens that pose serious threat to public health and challenge to researchers for discovering novel antifungal agents. Natural products from the members of phylum actinobacteria are the promising source of antibiotics including antifungal agents. Twenty-seven morphologically different actinobacterial cultures were isolated from the forest soils of Sabarimala, Kerala and Lucknow, Uttar Pradesh. Actinobacterial strain LA34 showed promising antifungal activity when screened against Candida albicans and Cryptococcus neoformans, hence selected as potential strain. Antifungal compounds were produced from the strain LA34 using agar surface fermentation and its extraction was done using ethyl acetate and methanol. Results of cultural, microscopic and physiological characteristics as well as cell wall amino acid and sugars analysis revealed that the strain LA34 was nonstreptomyces or rare actinobacterium. Various carbon sources, nitrogen sources and minerals were found to influence antifungal compound production by the strain LA34. The present study concluded that the rare actinobacterial strain LA34 isolated from Lucknow forest soil is a promising source for the isolation of antifungal compounds.

scholarly journals High Efficiency Drug Repurposing Design for New Antifungal Agents

2019 ◽  
Vol 2 (2) ◽  
pp. 31 ◽  
Author(s):  
Jong H. Kim ◽  
Kathleen L. Chan ◽  
Luisa W. Cheng ◽  
Lisa A. Tell ◽  
Barbara A. Byrne ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
High Efficiency ◽  
Intervention Strategy ◽  
Drug Repurposing ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Alternative Intervention ◽  
Combined Application

Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated “chemosensitization” as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen Aspergillus fumigatus. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.

scholarly journals IN VITRO AND IN VIVO ANTIFUNGAL ACTIVITY OF ALKALOID 3,5-bis(4,4’’-dimethoxy- [1,1’:2’,1’’-terphenyl]-4’-yl)-4H-pyrazole-4,4-diol FROM DERRIS INDICA (LAM) BENNETT SEEDS

2021 ◽  
pp. 133-140
Author(s):  
NUZHAT TABASSUM ◽  
VIDYASAGAR G. M. ◽  
RAGHUNANDAN D ◽  
SHIVAKUMAR I
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Hexane Extract ◽  
In Vivo Studies ◽  
Antifungal Compound ◽  
In Vivo Evaluation ◽  
Derris Indica

Objectives: The aim of the present study is to isolate an antifungal compound from Derris indica (Lam) Bennett seed oil with various solvents and evaluation of its antifungal activity against the clinical species of Candida. Methods: D. indica seed hexane extract was tested against Trichophyton rubrum, Trichophyton tonsurans and Candida albicans. Hexane extract was fractioned using different solvents through column chromatography (CC). Isolated compound D1 was identified and characterized using ultraviolet, Fourier-transform infrared, 1HNMR, and mass spectroscopy. In vitro evaluation of D1 carried out against 12 Candida strains. In vivo evaluation of D1 carried out against T. rubrum, T. tonsurans, and C. albicans using an excision wound healing model on male Wistar rats. Results: Different concentrations of hexane extract showed antimicrobial activity against tested microorganism with varying minimum inhibitory concentration values. On fractionation with hexane-petroleum ether through CC, it yielded a crystalline fraction. Compound D1 characterized as a 3,5-bis (4,4’’-dimethoxy-[1,1’: 2’,1’’-terphenyl]-4’-yl)-4H-pyrazole-4,4-diol. A novel alkaloid compound from D. indica is a new report and proved to be inhibitory against C. albicans MTCC 3017 (14.83±0.28), MTCC 1637 (16.0±0.0), Candida glabrata MTCC 3814 (16.83±0.28) and MTCC 3014 (16.66±0.57), Candida tropicalis MTCC 230 (20.0±0.0), MTCC 1406 (12.33±0.57). C. glabrata MTCC 3981 was found to be resistant to the compound. In vivo studies showed no visual symptoms at the end of treatment indicating the therapeutic property of the compound. Conclusion: The D1 was found to be effective against human fungal pathogens and can be used as a base molecule in designing new antifungal drugs.

scholarly journals In Vitro Antifungal Activity of Luliconazole, Efinaconazole, and Nine Comparators Against Aspergillus and Candida Strains Isolated from Otomycosis

2021 ◽  
Vol 14 (4) ◽  
Author(s):  
Gholamreza Shokoohi ◽  
Reza Rouhi ◽  
Mohammad Etehadnezhad ◽  
Bahram Ahmadi ◽  
Javad Javidnia ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Geometric Mean ◽  
Antifungal Drugs ◽  
High Recurrence Rate ◽  
Broth Microdilution ◽  
In Vitro Antifungal Activity

Background: Aspergillus and Candida species are the most commonly identified fungal pathogens in otomycosis. However, we usually encounter some difficulties in its treatment because many patients show resistance to antifungal agents and present a high recurrence rate. Objectives: The current research was conducted to compare the in vitro activities of luliconazole (LUL), and efinaconazole (EFN) and the nine comparators on Aspergillus and Candida strains isolated from otomycosis. Methods: The in vitro activities of nine common antifungal drugs (amphotericin B (AMB), voriconazole (VRC), fluconazole (FLU), itraconazole (ITC), ketoconazole (KTO), clotrimazole (CLO), nystatin (NYS), terbinafine (TRB), and caspofungin (CAS)) and two novel new azoles (LUL and EFN) against of 108 clinical isolates of Aspergillus and Candida species obtained from otomycosis were assessed according to the CLSI broth microdilution document. Results: The LUL and EFN had the geometric mean minimum inhibitory concentrations (GM MICs) of 0.098 and 0.109 μg/mL against all Aspergillus strains, respectively. Furthermore, the GM MICs of all Candida isolates for LUL, EFN, CAS, CLO, VRC, AMB, ITC, KTO, FLU, NYS, and TRB were calculated to be 0.133, 0.144, 0.194, 0.219, 0.475, 0.537, 0.655, 1.277, 4.905, 9.372, and 13.592 μg/mL, respectively. Additionally, 6 (35.29%), 2 (11.7%), and 1 (5.88%) Candida isolates were resistant to FLU, CAS, and VRC, respectively. Conclusions: As the findings indicated, LUL and EFN showed the lowest GM MIC values against the examined species. Accordingly, these novel imidazole and triazole antifungal agents can be regarded as proper candidates for the treatment of otomycosis caused by Aspergillus and Candida strains.

scholarly journals A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Leslie A. Rank ◽  
Naomi M. Walsh ◽  
Runhui Liu ◽  
Fang Yun Lim ◽  
Jin Woo Bok ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Mammalian Cells ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Antifungal Compound ◽  
Human Pathogens ◽  
Host Defense Peptides ◽  
Content Type ◽  
Highly Active ◽  
Multiple Species

ABSTRACT Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of Candida and Cryptococcus, reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of Aspergillus, including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies.

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 Identification of Fungal Pathogens in Otomycosis and Their Drug Sensitivity: Our Experience

2018 ◽  
Vol 22 (04) ◽  
pp. 400-403 ◽  
Author(s):  
Khaled Ali ◽  
Mahmood Hamed ◽  
Hameda Hassan ◽  
Amira Esmail ◽  
Abeer Sheneef
Keyword(s):  
Enzymatic Activity ◽  
Candida Species ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Antifungal Susceptibility Testing ◽  
Antifungal Drugs ◽  
High Recurrence Rate ◽  
Fungal Culture

Introduction Otomycosis is a common problem in otolaryngology practice. However, we usually encounter some difficulties in its treatment because many patients show resistance to antifungal agents, and present high recurrence rate. Objectives To determine the fungal pathogens that cause otomycosis as well as their susceptibility to the commonly used antifungal agents. Additionally, to discover the main reasons for antifungal resistance. Methods We conducted an experimental descriptive study on 122 patients clinically diagnosed with otomycosis from April 2016 to April 2017. Aural discharge specimens were collected for direct microscopic examination and fungal culture. In vitro antifungal susceptibility testing was performed against the commonly used antifungal drugs. We tested the isolated fungi for their enzymatic activity. Results Positive fungal infection was found in 102 samples. The most common fungal pathogens were Aspergillus and Candida species, with Aspergillus niger being the predominant isolate (51%). The antifungal susceptibility testing showed that mold isolates had the highest sensitivity to voriconazole (93.48%), while the highest resistance was to fluconazole (100%). For yeast, the highest sensitivity was to nystatin (88.24%), followed by amphotericin B (82.35%), and the highest resistance was to terbinafine (100%), followed by Itraconazole (94.12%). Filamentous fungi expressed a high enzymatic ability, making them more virulent. Conclusion The Aspergillus and Candida species are the most common fungal isolates in otomycosis. Voriconazole and Nystatin are the medications of choice for the treatment of otomycosis in our community. The high virulence of fungal pathogens is owed to their high enzymatic activity. Empirical use of antifungals should be discouraged.

scholarly journals Antifungal activity of various plant oils against yeast isolates from ICU patients

2017 ◽  
Vol 5 (7) ◽  
pp. 3227
Author(s):  
Akansha Suman ◽  
Sapna Chauhan ◽  
Suman Lata ◽  
Rajeev K. Sharma
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Tertiary Care ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Plant Oils ◽  
Clove Oil ◽  
Icu Patients ◽  
Long Term Treatment

Background: To evaluate the in-vitro antifungal activity of various essential plant oils against yeast species.Methods: The present study was a prospective study conducted in Department of Microbiology along with Department of Pharmacology at Tertiary care teaching hospital. Various clinical samples from ICU patients were inoculated on Sabourauds Dextrose Agar (SDA) in accordance with the standard methods. Yeast isolates were recovered and identified as per standard recommended procedure. The antifungal activity of plant oils against these isolated yeasts was determined using disc diffusion method. The results were interpreted as <9mm-inactive, 9-12mm-partially active, 13-18mm-very active. Fluconazole and Itraconazole were taken as control drugs.Results: The various yeast isolated were C. albicans, C. tropicals, C. krusei, C. glabrata, C. gulliermondi, C. keyfr, Cryptococcus and Tricosporon. Among essential plant oils, Cinnamon oil and clove oil showed high activity against all isolated yeast species. Olive oil showed least antifungal activity. Fluconazole was resistant in all yeast isolates, while Itraconazole was sensitive to all yeast isolates. Sensitivity of cinnamon and clove oil was statistically significant than Itraconazole.Conclusions: To conclude present study shows the potential of essential plant oils as newer therapeutic alternatives to antifungal drugs. These may be used in combination with antifungal agents to overcome drug resistance, adverse effects and in shortening the long-term treatment with antifungal drugs. Thus, these essential plant oils can be used in future as antifungal agents in azoles resistant strains.

scholarly journals THERAPEUTIC INDICES OF SOME ANTIFUNGAL ORGANIC COMPOUNDS

2021 ◽  
pp. 115-117
Author(s):  
EUGENE SEBASTIAN J. NIDIRY
Keyword(s):  
Antifungal Activity ◽  
Organic Compounds ◽  
Chain Length ◽  
Carbon Chain ◽  
Carbon Chain Length ◽  
Antifungal Compound ◽  
Antifungal Compounds ◽  
Potato Dextrose Agar Medium ◽  
Mammalian Toxicity ◽  
The Relationship

Objective: The objective of the study was to evaluate the therapeutic indices (TIs) some antifungal organic compounds and to compare their safety. Methods: TIs of 55 organic compounds were evaluated by dividing their mammalian toxicity values given as median lethal doses ([mg/kg] rat, oral) collected from literature by experimentally determined fungitoxicity values evaluated as median effective concentration (EC50 [mg/L]) for the mycelial growth inhibition of Colletotrichum gloeosporioides on potato dextrose agar medium. Results: Large variations in TIs are observed in different classes of compounds, namely, alcohols, carboxylic acids, phenols, esters, and aldehydes. The relationship between carbon chain length of saturated monohydric alcohols and mammalian toxicity shows that toxicity increases from chain length 1 to 5, declines from 5 to 6, increases from 6 to 7, and steadily declines from 7 to 10. Thus, the relationship is by and large parabolic. The relationship between carbon chain length and molar antifungal activity is also parabolic. In spite of this, large differences are found in TIs making 1-decanol (TI=42.1) a very safe antifungal compound and 1-pentanol (TI=0.17) a hazardous antifungal compound. This is because mammalian toxicity reaches a maximum around carbon chain length of 5, while in the case of antifungal activity, it reaches a maximum around carbon chain length of 10. Conclusions: Among the 55 compounds, whose TIs were evaluated, some compounds with high TIs (>10) which can be considered safe as antifungal compounds are citronellol, geraniol, 1-decanol, 1-octanol, phenyl acetaldehyde, methyl anthranilate, 1-naphthol, 2-naphthol, and propionic acid. Some compounds with low TIs (<0.50) which can be considered hazardous as antifungal compounds are resorcinol, hydroquinone, oxalic acid, and acetyl acetone.

scholarly journals Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Gina Wall ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Alternative Pathway ◽  
Drug Repurposing ◽  
Pathogenic Fungi ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Antifungal Drugs ◽  
Promising Alternative

ABSTRACT Fungal organisms are ubiquitous in nature, and progress of modern medicine is creating an expanding number of severely compromised patients susceptible to a variety of opportunistic fungal infections. These infections are difficult to diagnose and treat, leading to high mortality rates. The limited antifungal arsenal, the toxicity of current antifungal drugs, the development of resistance, and the emergence of new multidrug-resistant fungi, all highlight the urgent need for new antifungal agents. Unfortunately, the development of a novel antifungal is a rather long and expensive proposition, and no new classes of antifungal agents have reached the market in the last 2 decades. Drug repurposing, or finding new indications for old drugs, represents a promising alternative pathway to drug development that is particularly appealing within the academic environment. In the last few years, there has been a growing interest in repurposing approaches in the antifungal arena, with multiple groups of investigators having performed screenings of different repurposing libraries against different pathogenic fungi in search for drugs with previously unrecognized antifungal effects. Overall, these repurposing efforts may lead to the fast deployment of drugs with novel antifungal activity, which can rapidly bring benefits to patients, while at the same time reducing health care costs.

Ruthenium based antifungal compounds and their activity

2021 ◽  
Vol 25 (7) ◽  
pp. 177-182
Author(s):  
Rahul Kanaoujiya ◽  
Shekhar Srivastava
Keyword(s):  
Antifungal Activity ◽  
Drug Design ◽  
Ruthenium Complexes ◽  
Chemical Properties ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Attractive Alternative ◽  
Antifungal Compounds ◽  
Lower Toxicity ◽  
Ruthenium Compounds

Ruthenium is recognized as a highly attractive alternative to platinum since the toxicity of many ruthenium compounds is lower and some complexes are quite selective for antifungal drugs. Ruthenium has various chemical properties these chemical properties are very useful for antifungal drug design. Ruthenium compounds have several types of advantages as antifungal drugs because of lower toxicity. . Ruthenium has unique properties making it of particularly use as fungal in drug design specially in antifungal drugs. Several types of ruthenium complexes and their antifungal activity standards are described here.

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