scholarly journals A review on antifungal agents against Candida albicans and Aspergillus niger

2021 ◽  
Vol 2 (1) ◽  
pp. 042-054
Author(s):  
Vishnuvardhini R ◽  
Priya R Iyer
Keyword(s):  
Cell Wall ◽  
Natural Products ◽  
Candida Albicans ◽  
Aspergillus Niger ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Natural Compounds ◽  
Synthetic Compounds ◽  
Synthetic Drugs

Candidiasis is the fungal infection caused by Candida albicans. It causes different type of candidiasis infections in the blood, heart, eyes, brain, bones also other parts of our body. Different types of candidiasis are vaginal candidiasis, pulmonary candidiasis, oral candidiasis. It may be acute or chronic. It can be cured by using natural compounds or synthetic compounds or semisynthetic compounds. Apergillosis is the fungal infections in human caused by Aspergillus niger. Aspergillosis infections are classified into allergic pulmonary sinusitis, cutaneous aspergillosis, invasive aspergillosis, chronic necrotising pulmonary aspergillosis can be cured by using synthetic compounds like intravenous injections, oral medicines of capsules, tropical medicines like creams and some other natural products from plants. Natural products like saponins, flavonoids, alkaloids, xanthones, lectins and polypeptides, quinones, terpenoids, coumarins, essential oils and other compounds are the secondary metabolites extracted from the plants. Those plants are effective against fungal infections. Synthetic drugs like Azole group of drugs composed of imidazoles which includes miconazole, clotrimazole, ketoconazole, and triazoles include itraconazole, Posaconazole, isavuconazole are used to inhibit the ergosterol synthesis of cell membrane of fungi. Echinocandins are antifungal agent and it is used to disrupt the cell wall of fungi and inhibiting the synthesis of beta- 1,3 glucan fungal cell wall. Echinocandins are classified into caspofungin, anidulafungin, micafungin which having antifungal activity and amphotericin B used to treat both candidiasis and aspergillosis. Combination of drugs like synthetic drugs and natural compounds used to treat Candidiasis and Aspergillosis. Comparison and effectiveness of drugs depends upon the infections they are getting affected. Amphotericin B and azole group of drugs are commonly more effective than other group of drugs, but ketoconazole is widely used. Adverse effects of antifungal agents include, skin rashes, irritation, itching, nausea and vomiting, fever, abdominal pain, muscle and joint pain, etc.

Potent Chitin Synthase Inhibitors from Plants

2020 ◽  
Vol 16 (1) ◽  
pp. 58-63
Author(s):  
Amrutha Vijayakumar ◽  
Ajith Madhavan ◽  
Chinchu Bose ◽  
Pandurangan Nanjan ◽  
Sindhu S. Kokkal ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Caenorhabditis Elegans ◽  
Aspergillus Niger ◽  
Small Molecules ◽  
Tip Growth ◽  
Chitin Synthase ◽  
Chitin Synthesis ◽  
Hyphal Tip Growth ◽  
Hyphal Tip

Background: Chitin is the main component of fungal, protozoan and helminth cell wall. They help to maintain the structural and functional characteristics of these organisms. The chitin wall is dynamic and is repaired, rearranged and synthesized as the cells develop. Active synthesis can be noticed during cytokinesis, laying of primary septum, maintenance of lateral cell wall integrity and hyphal tip growth. Chitin synthesis involves coordinated action of two enzymes namely, chitin synthase (that lays new cell wall) and chitinase (that removes the older ones). Since chitin synthase is conserved in different eukaryotic microorganisms that can be a ‘soft target’ for inhibition with small molecules. When chitin synthase is inhibited, it leads to the loss of viability of cells owing to the self- disruption of the cell wall by existing chitinase. Methods: In the described study, small molecules from plant sources were screened for their ability to interfere with hyphal tip growth, by employing Hyphal Tip Burst assay (HTB). Aspergillus niger was used as the model organism. The specific role of these small molecules in interfering with chitin synthesis was established with an in-vitro method. The enzyme required was isolated from Aspergillus niger and its activity was deduced through a novel method involving non-radioactively labelled substrate. The activity of the potential lead molecules were also checked against Candida albicans and Caenorhabditis elegans. The latter was adopted as a surrogate for the pathogenic helminths as it shares similarity with regard to cell wall structure and biochemistry. Moreover, it is widely studied and the methodologies are well established. Results: Out of the 11 compounds and extracts screened, 8 were found to be prospective. They were also found to be effective against Candida albicans and Caenorhabditis elegans. Conclusion: Purified Methyl Ethyl Ketone (MEK) Fraction1 (F1) of Coconut (Cocos nucifera) Shell Extract (COSE) was found to be more effective against Candida albicans with an IC50 value of 3.04 μg/mL and on L4 stage of Caenorhabditis elegans with an IC50 of 77.8 μg/mL.

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

2020 ◽  
Vol 63 (2) ◽  
pp. 7-17
Author(s):  
Evelyn Rivera-Toledo ◽  
Alan Uriel Jiménez-Delgadillo ◽  
Patricia Manzano-Gayosso
Keyword(s):  
Antifungal Activity ◽  
Key Words ◽  
Secondary Metabolism ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Variable Number ◽  
Therapeutic Failure ◽  
Morbidity And Mortality ◽  
Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

scholarly journals Sublethal Injury and Resuscitation of Candida albicans after Amphotericin B Treatment

2003 ◽  
Vol 47 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Robert S. Liao ◽  
Robert P. Rennie ◽  
James A. Talbot
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Sybr Green ◽  
Sequential Treatment ◽  
Tetrazolium Salt ◽  
Fungal Cell ◽  
Sublethal Injury

ABSTRACT Amphotericin B treatment was previously shown to inhibit Candida albicans reproduction and reduce the fluorescence of vitality-specific dyes without causing a corresponding increase in the fluorescence of the mortality-specific dyes bis-(1,3-dibutylbarbituric acid)trimethine oxonol and SYBR Green Ι. In the present study, we have confirmed these results and have shown that the numbers of CFU are reduced by 99.9% by treatment with 0.5 μg of amphotericin B per ml for 10 h at 35°C. This reduction was not due to fungal cell death. First, the level of reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide increased in the presence of concentrations of amphotericin B that caused greater than 90% reductions in the numbers of CFU. Second, fungal cells treated with amphotericin B at a concentration of 0.5 μg/ml were resuscitated by further incubation at 22°C for 15 h in the continued presence of amphotericin B. Third, recovery of the ability to replicate was prevented by sequential treatment with 20 μg of miconazole per ml, which also increased the fluorescence of mortality-specific dyes to near the maximal levels achieved with 0.9 μg of amphotericin B per ml. Sequential treatment with fluconazole and flucytosine did not increase the levels of staining with the mortality-specific dyes. Itraconazole was less effective than ketoconazole, which was less effective than miconazole. The practice of equating the loss of the capacity of C. albicans to form colonies with fungal cell death may give incorrect results in assays with amphotericin B, and the results of assays with caution with other antifungal agents that are lipophilic or that possess significant postantifungal effects may need to be interpreted.

A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joelle Ngo Hanna ◽  
Boris D. Bekono ◽  
Luc C. O. Owono ◽  
Flavien A. A. Toze ◽  
James A. Mbah ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Functional Groups ◽  
Atomic Composition ◽  
Synthetic Compounds ◽  
Chemical Libraries ◽  
Synthetic Drugs ◽  
Drugs Analysis ◽  
Chemical Class

Abstract In the quest to know why natural products (NPs) have often been considered as privileged scaffolds for drug discovery purposes, many investigations into the differences between NPs and synthetic compounds have been carried out. Several attempts to answer this question have led to the investigation of the atomic composition, scaffolds and functional groups (FGs) of NPs, in comparison with synthetic drugs analysis. This chapter briefly describes an atomic enumeration method for chemical libraries that has been applied for the analysis of NP libraries, followed by a description of the main differences between NPs of marine and terrestrial origin in terms of their general physicochemical properties, most common scaffolds and “drug-likeness” properties. The last parts of the work describe an analysis of scaffolds and FGs common in NP libraries, focusing on huge NP databases, e.g. those in the Dictionary of Natural Products (DNP), NPs from cyanobacteria and the largest chemical class of NP – terpenoids.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals Spatial Distribution of a Porphyrin-Based Photosensitizer Reveals Mechanism of Photodynamic Inactivation of Candida albicans

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Voit ◽  
Fabian Cieplik ◽  
Johannes Regensburger ◽  
Karl-Anton Hiller ◽  
Anita Gollmer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Cell Envelope ◽  
Antimicrobial Photodynamic Therapy ◽  
Fungal Cell ◽  
Before And After ◽  
Antifungal Action ◽  
Complete Cell ◽  
Further Development

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans.

scholarly journals Distribution and antifungal susceptibility of Candida species in patients with increased risk for fungal infections

2016 ◽  
Vol 62 (1) ◽  
pp. 65-76
Author(s):  
Gordana Mirchevska ◽  
Maja Jurhar Pavlova ◽  
Elena Trajkovska-Dokic ◽  
Zaklina Cekovska ◽  
Gordana Jankoska ◽  
...  
Keyword(s):  
Blood Culture ◽  
Amphotericin B ◽  
Critically Ill Patients ◽  
Candida Species ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Clinical Specimens ◽  
Fourth Group ◽  
Increased Risk

Candida species are opportunistic yeasts that can be a serious threat for immunocompromised and critically ill patients, and a cause for increased morbidity and mortality in hospitalized patients. The aim of this study was to determine the frequency and distribution of different Candida species in clinical specimens in patients with increased risk for fungal infections, and to determine the antifungal susceptibility profile of invasive Candida species to antifungal agents. During a two year period, clinical specimens from 120 patients divided into 4 groups were analysed at the Institute of microbiology and parasitology, Faculty of Medicine, Skopje, Republic of Macedonia. Each of these 4 groups consisted of specimens from 30 patients, with primary immune deficiency, critically ill patients treated in the intensive care units (ICU), patients with mucosal candidiasis only, and patients with cystic fibrosis. All specimens were investigated with conventional mycological methods. Identification of Candida species was performed with VITEK-2 system (bioMérieux, France). E-test strips of fluconazole, voriconazole, amphotericin B and caspofungin (AB bioMerieux, France) were used for determination of the antifungal susceptibility profile. In this study, a total of 115 isolates of Candida species were confirmed in different clinical specimens (91 isolates from mucosal surfaces and 24 isolates from blood culture). Colonisation of mucosal membranes of gastrointestinal, respiratory and/or urinary tracts was registered in 56.67% (17/30), 56.67% (17/30), 90% (27/30) and 100% (30/30) of the specimens in the first, second, third and fourth group respectively. In all four groups of patients, the following Candida species were confirmed: C. albicans - 55%, C. glabrata - 17.6%, C. parapsilosis - 7.7%, C. tropicalis - 6.6%, unidentified Candida species - 4.4%, C. dubliniensis - 3.3%, C. kefyr - 2.2%, and one isolate of C. rugosa, C. pelliculosa and C. krusei each. Positive blood culture was registered in 23.33% specimens from the first group, 43.33% in the second group, 23.08% of the third group, and in one specimen of the fourth group. The most frequent isolates from blood culture were C. tropicalis and C. krusei, followed by C. albicans, C. parapsilosis and C. tropicalis, and in the second group C. albicans and C. pelliculosa were equally distributed, followed by C. parapsilosis and C. glabrata. All invasive isolates of Candida species were susceptible to amphotericin B, voriconazole and caspofungin. Resistance to fluconazole was registered in 8.3% (2/24) of all confirmed Candida species. Dose-dependent susceptibility to fluconazole was confirmed in 46% (11/24) of the isolates. Our study confirms high prevalence of colonisation and candidemia with non-albicans Candida species. Resistance to antifungal agents was registered only in two isolates of C. krusei. An epidemiological study is necessary for surveillance of dynamics of candidemia and antifungal susceptibility profile of invasive isolates of Candida species in our patients.

scholarly journals Candida albicans Sterol C-14 Reductase, Encoded by the ERG24 Gene, as a Potential Antifungal Target Site

2002 ◽  
Vol 46 (4) ◽  
pp. 947-957 ◽  
Author(s):  
N. Jia ◽  
B. Arthington-Skaggs ◽  
W. Lee ◽  
C. A. Pierson ◽  
N. D. Lees ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Brefeldin A ◽  
Agricultural Applications ◽  
Mouse Model System ◽  
Cellular Inhibitors ◽  
Germ Tubes ◽  
Doubling Times

ABSTRACT The incidence of fungal infections has increased dramatically, which has necessitated additional and prolonged use of the available antifungal agents. Increased resistance to the commonly used antifungal agents, primarily the azoles, has been reported, thus necessitating the discovery and development of compounds that would be effective against the major human fungal pathogens. The sterol biosynthetic pathway has proved to be a fertile area for antifungal development, and steps which might provide good targets for novel antifungal development remain. The sterol C-14 reductase, encoded by the ERG24 gene, could be an effective target for drug development since the morpholine antifungals, inhibitors of Erg24p, have been successful in agricultural applications. The ERG24 gene of Candida albicans has been isolated by complementation of a Saccharomyces cerevisiae erg24 mutant. Both copies of the C. albicans ERG24 gene have been disrupted by using short homologous regions of the ERG24 gene flanking a selectable marker. Unlike S. cerevisiae, the C. albicans ERG24 gene was not required for growth, but erg24 mutants showed several altered phenotypes. They were demonstrated to be slowly growing, with doubling times at least twice that of the wild type. They were also shown to be significantly more sensitive to an allylamine antifungal and to selected cellular inhibitors including cycloheximide, cerulenin, fluphenazine, and brefeldin A. The erg24 mutants were also slightly resistant to the azoles. Most importantly, erg24 mutants were shown to be significantly less pathogenic in a mouse model system and failed to produce germ tubes upon incubation in human serum. On the basis of these characteristics, inhibitors of Erg24p would be effective against C. albicans.

Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans

2020 ◽  
Author(s):  
Lisa Kirchhoff ◽  
Silke Dittmer ◽  
Ann-Kathrin Weisner ◽  
Jan Buer ◽  
Peter-Michael Rath ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Laser Scanning ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pathogenic Fungus ◽  
Antifungal Drugs ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antibiofilm Activity

Abstract Objectives Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed. Methods Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm. Results Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were ≤4 mg/L. On mature biofilm the MBECs of olorofim and voriconazole were higher than the previously determined MICs against planktonic cultures. In contrast, amphotericin B and especially micafungin did not exhibit sufficient antibiofilm activity against L. prolificans. Conclusions To our knowledge, this is the first study demonstrating the antibiofilm potential of olorofim against the human pathogenic fungus L. prolificans.

Pharmacokinetics of Antifungal Agents

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 380-382 ◽  
Author(s):  
A. Fabris ◽  
M. V. Pellanda ◽  
C. Gardin ◽  
A. Contestabile ◽  
R. Bolzonella
Keyword(s):  
Abdominal Pain ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Peritoneal Fluid ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Intraperitoneal Administration ◽  
Point Of View ◽  
Severe Abdominal Pain ◽  
Fungal Peritonitis

The authors have evaluated the pharmacokinetics of four antifungal agents used in the therapy of fungal peritonitis. Amphotericin B (Amph B) poorly diffuses from blood into peritoneal fluid, which Intraperitoneal administration induces severe abdominal pain. 5-Fluorocytosine (5FC) easily crosses peritoneum, but resistance may appear when the drug is used alone. Ketoconazole (K) poorly penetrates into peritoneal fluid, while Fluconazole (F), used per os or intraperitoneally, shows a good antifungal activity both in serum and In the peritoneal fluid. In conclusion, from a pharmacokinetic point of view, all the antifungal agents examined, perhaps with the exception of F, do not offer, when used alone, sufficient guarantees In curing peritonitis. Therefore, for treating fungal infections in CAPD, drug combinations such as AmphB + 5FC, K + 5FC or 5FC + F have to be used.

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