scholarly journals Synthesis and antifungal activity of new O-alkylamidoximes

2021 ◽  
Vol 37 ◽  
pp. e37049
Author(s):  
Maria Verônica Sales Barbosa ◽  
Alana Karoline Penha Nascimento ◽  
Rodrigo Ribeiro Alves Caiana ◽  
Cosme Silva Santos ◽  
Wylly Araújo Oliveira ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Therapeutic Agents ◽  
New Drugs ◽  
Moderate Activity ◽  
Relevant Issue ◽  
New Class ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
New Compounds

The continuous prospection for molecules that may be useful in the development of new therapeutic agents is a highly relevant issue, mainly because the launch of new drugs on the market does not accompany the emergence of new resistant microorganisms. In this context, this work describes the synthesis of new O-alkylamidoximes and the evaluation of its antifungal activity. The new O-alkylamidoximes were prepared using easy synthetic protocols and tested against three Candida species using the broth microdilution method. The synthesized compounds were obtained in moderate to good yields in high purity and without any observable decomposition. All tested compounds shown moderate antifungal activity against at least one strain of Candida. Despite the moderate activity of the new compounds, this was the first report involving the antifungal activity of O-alkylamidoximes. In view of the low chemotherapy arsenal and the development of fungal strains resistant to traditional antifungal agents, the present study opens new possibilities for the preparation of a new class of more active antifungal agents.

scholarly journals Structural and Bioactivity Characterization of Filipin Derivatives from Engineered Streptomyces filipinensis Strains Reveals Clues for Reduced Haemolytic Action

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 413
Author(s):  
Eva G. Barreales ◽  
Ángel Rumbero ◽  
Tamara D. Payero ◽  
Antonio de Pedro ◽  
Ester Jambrina ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
New Drugs ◽  
Metabolic Intermediates ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Opportunistic Pathogenic

The rise in the number of immunocompromised patients has led to an increased incidence of fungal infections, with high rates of morbidity and mortality. Furthermore, misuse of antifungals has boosted the number of resistant strains to these agents; thus, there is urgent need for new drugs against these infections. Here, the in vitro antifungal activity of filipin III metabolic intermediates has been characterized against a battery of opportunistic pathogenic fungi—Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, Trichosporon cutaneum, Trichosporon asahii, Aspergillus nidulans, Aspergillus niger, and Aspergillus fumigatus—using the Clinical and Laboratory Standards Institute broth microdilution method. Structural characterization of these compounds was undertaken by mass spectrometry (MS) and nuclear magnetic resonance (NMR) following HPLC purification. Complete NMR assignments were obtained for the first time for filipins I and II. In vitro haemolytic assays revealed that the haemolytic action of these compounds relies largely on the presence of a hydroxyl function at C26, since derivatives lacking such moiety show remarkably reduced activity. Two of these derivatives, 1′-hydroxyfilipin I and filipin I, show decreased toxicity towards cholesterol-containing membranes while retaining potent antifungal activity, and could constitute excellent leads for the development of efficient pharmaceuticals, particularly against Cryptococcosis.

scholarly journals In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata

2004 ◽  
Vol 48 (9) ◽  
pp. 3317-3322 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Monia Maracci ◽  
Annette W. Fothergill ◽  
Isabella Baldassarri ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Beneficial Effects ◽  
Synergistic Interactions ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Disk Diffusion Assay ◽  
Combination Regimens

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

scholarly journals Evaluation of a Modified EUCAST Fragmented-Mycelium Inoculum Method forIn VitroSusceptibility Testing of Dermatophytes and the Activity of Novel Antifungal Agents

2015 ◽  
Vol 59 (6) ◽  
pp. 3675-3682 ◽  
Author(s):  
B. Risslegger ◽  
C. Lass-Flörl ◽  
G. Blum ◽  
M. Lackner
Keyword(s):  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Preparation Method ◽  
Antifungal Susceptibility ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Inoculum Preparation ◽  
Minimal Effective Concentration

ABSTRACTFor antifungal susceptibility testing of nonsporulating or poorly sporulating dermatophytes, a fragmented-mycelium inoculum preparation method was established and compared to broth microdilution testing according to CLSI and EUCAST guidelines. Moreover, thein vitroactivity of new antifungal agents against dermatophytes was evaluated. Agreement between the mycelial inoculum method and the CLSI broth microdilution method was high (93% to 100%). Echinocandins (minimal effective concentration [MEC], ≤0.5 mg/liter) and posaconazole (MIC, ≤3.00 mg/liter) showed good activity against all tested dermatophytes.

scholarly journals Evaluation of semisolid agar method for antifungal susceptibility test of T. rubrum

2016 ◽  
Vol 7 (1) ◽  
pp. 11
Author(s):  
Sultana Razia ◽  
Shahida Anwar ◽  
Md. Ruhul Amin Miah ◽  
Najmun Nahar ◽  
Ripon Barua
Keyword(s):  
Antifungal Agents ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
Test Method ◽  
Susceptibility Test ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Antifungal Susceptibility Test ◽  
Mic Value

<p><strong>Background:</strong> With increasing fungal disease many newer antifungal drugs are available with different spectrum of activ­ity. Antifungal susceptibility test will help clinicians for selection of effective drug and thereby treatment of patient.<strong> </strong></p><p><strong>Objective:</strong> The study was undertaken to perform a simple screening drug susceptibility test of T. rnbrum by Semi Solid Agar Antifungal Susceptibility (SAAS) <strong></strong></p><p><strong>Method:</strong> Perfonnance of susceptibility method was assessed by comparing the MICs of three commonly prescribed antifungal agents namely- tluconazole (FCZ), itraconazole (ITZ) and terbinafine (TER) to the CLSI (Clinical and Laboratory Standard Institute) recommended M-38, a broth microdilution method. <strong></strong></p><p><strong>Results:</strong> In SAAS method, among twenty nine T. rubrum, twenty five (86.2%) were susceptible (MIC range 0.5-64 µg/ml) to Fluconazole (FCZ) and four (13.7%) were resistant (MIC value &gt;64 µg/ml). In broth microdilution method, among twenty nine T. rubrum, twenty six (89.6%) were susceptible (MIC range 0.3-64 µg/ml) to FCZ and three (10.3%) were resistant (MIC value &gt;64 µg/ml). In case of both ITZ and TER, all were susceptible (MIC range 0.3-64 µg/ml) to both methods. The SAAS method demonstrated the susceptibility pattern of T. rubrum against FCZ, ITZ and TER usually within 72 to 96 hours after organism isolation and results were concordance with the results of CLSI broth microdilution method. <strong></strong></p><p><strong>Conclusion:</strong> Though it is a newer method with proper standardization of the test method, SAAS method is simple and easily applicable screening method for susceptibility testing of antifungal agents against dermatophytes in any microbiology laboratories.</p>

Investigation of a New Compound, B.W.203, and of Chlorpromazine in the Treatment of Psychosis

1958 ◽  
Vol 104 (436) ◽  
pp. 749-757 ◽  
Author(s):  
B. G. Fleming ◽  
J. D. C. Currie
Keyword(s):  
Mental Illness ◽  
Scientific Theory ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
New Drugs ◽  
Clinical Test ◽  
Empirical Methods ◽  
Phenothiazine Derivatives ◽  
Widespread Application ◽  
New Compounds

The discovery of chlorpromazine in the Rhône-Poulenc-Spécia laboratories in France, and the subsequent early clinical studies which were carried out in that country, for example in 1952 by Hamon et al. (5) and in 1953 by Delay and Deniker (1), eventually resulted in the enthusiastic and widespread application of this compound in the field of clinical psychiatry. Chemists and pharmacologists, in many countries, have been actively engaged during the ensuing years in the search for new compounds which might prove to be more potent therapeutic agents than chlorpromazine in the treatment of mental illness. One of the tangible manifestations of their labours is the present crop of “tranquillizers” which are being extensively used in the treatment of neurosis and psychosis. Whereas opinion may be divided with regard to the real or specific value of any one of these new drugs, few would disagree with the contention that none of them is ideal. Despite the considerable number and variety of phenothiazine derivatives and other new substances which have been developed as a result of extensive research, chlorpromazine has retained much of its original therapeutic reputation, in open competition with its rivals, down the years, and is still probably the most widely used tranquillizer today. This would seem to imply that no outstanding advance has been made since the early days of the new biochemical era in psychiatry. Valuable knowledge may have been obtained as a result of the application of scientific theory and empirical methods in this field, but in terms of effective therapeutic agents the results have been meagre, with the accent on quantity rather than quality. Nevertheless, a continued search is justifiable, and any new compound which holds forth promise must be put to a clinical test if final success is to be assured and if valuable therapeutic potential is not to be summarily dismissed or heedlessly cast aside.

scholarly journals New sulfone and sulfanyl derivatives with antifungal activity

2018 ◽  
pp. 175-184
Author(s):  
Małgorzata Gizińska ◽  
Marzena Połaska ◽  
Zbigniew Ochal ◽  
Monika Staniszewska
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
In Vitro Susceptibility ◽  
Microdilution Method ◽  
Alternative Approach ◽  
Broth Microdilution Method ◽  
Fungal Morphogenesis ◽  
In Vitro Susceptibility Testing ◽  
Base Structure

Introduction: Increasing occurrence of fungal infections raises the need to develop novel antifungal agents. In this context, an inhibition of morphological switch may provide an alternative approach to find compounds with a potential to control the Candida albicans infections. Methods: A series of 17 sulfone and sulfanyl derivatives was synthesized and evaluated for activity against the C. albicans wild type (SC5314, ATCC) and SAP-deficient mutant strains using the broth microdilution method M27-A3. Afterwards, phase-contrast microscopy was applied to evaluate the inhibition of fungal morphogenesis under the influence of randomly selected active compounds: 1, 5 and 6. Results: By in vitro susceptibility testing of C. albicans, we identified the effective antifungal agents displaying moderate-to-good activity. Newly synthesized sulfanyl and sulfone derivatives strongly inhibited the C. albicans morphogenetic transition under the hyphae inducing conditions. Conclusions: The leading compound 6 has the potential to be used as a base structure in antifungal drug development, however further structural optimalization and toxicity studies are required.

In vitro activity of BMS-181184 compared with those of fluconazole and amphotericin B against various candida spp.

1996 ◽  
Vol 40 (9) ◽  
pp. 2229-2231 ◽  
Author(s):  
H M Wardle ◽  
D Law ◽  
D W Denning
Keyword(s):  
High Resolution ◽  
Amphotericin B ◽  
Clinical Studies ◽  
Antifungal Agents ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
New Class ◽  
Microdilution Method

We compared the in vitro activity of BMS-181184, the first compound of a new class of antifungal agents, the pradimicins, with those of fluconazole and amphotericin B against 64 clinical isolates of Candida species. MICs were determined by a microdilution method with high resolution medium for BMS-181184 and fluconazole and antibiotic medium no. 3 with 2% glucose for amphotericin B. MICs of BMS-181184 for all yeasts were in the range of 0.78 to 12.5 micrograms/ml. BMS-181184 was active against isolates resistant to other antifungal agents, consistent with a novel mode of action. Minimum fungicidal concentrations for 16 isolates showed that BMS-181184 was fungicidal. Clinical studies are now required to confirm its activity.

Griseofulvin Derivatives: Synthesis, Molecular Docking and Biological Evaluation

2019 ◽  
Vol 19 (13) ◽  
pp. 1145-1161 ◽  
Author(s):  
Victor Kartsev ◽  
Athina Geronikaki ◽  
Anthi Petrou ◽  
Boris Lichitsky ◽  
Marina Kostic ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antifungal Activity ◽  
Organic Synthesis ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design And Synthesis ◽  
Microdilution Method ◽  
New Compounds ◽  
Better Than

Background:Griseofulvin - a mold metabolite produced by Penisilium griseofulvum is known as an antifungal drug.Objective:Thus, the goal of this paper is the design and synthesis of new griseofulvin derivatives and evaluation of their antifungal activity.Methods:Forty-two new compounds were synthesized using classical methods of organic synthesis and evaluated for their antimicrobial activity by microdilution method.Results:All forty-two new compounds exhibited very good activity against eight tested micromycetes with MIC ranging from 0.0075-0.055 mg/ml and MFC from 0.02-024 mg/ml. All compounds exhibited better activity than reference drugs ketoconazole (7-42 times) and bifonazole (3-16 fold). The most promising was compound 15. The most sensitive fungal was found to be T. viride, while the most resistant, as was expected, was A. fumigatus. It should be mentioned that most of compounds exhibited better activity than griseofulvin.:The molecular docking studies revealed that the most active compound have the same hydrophobic and H-bonding interactions with Thr276 residue observed for griseofulvin forming 3 hydrogen bonds while griseofulvin only one. In general, the molecular docking results coincide with experimental.Conclusion:Forty-two giseofulvin derivatives were designed, synthesized and evaluated for antimicrobial activity. These derivatives revealed good antifungal activity, better than reference drugs ketoconazole, bifonazole, and griseofulvin as well.

scholarly journals Antifungal Activity of Micafungin in Serum

2009 ◽  
Vol 53 (10) ◽  
pp. 4559-4562 ◽  
Author(s):  
Jun Ishikawa ◽  
Tetsuo Maeda ◽  
Itaru Matsumura ◽  
Masato Yasumi ◽  
Hidetoshi Ujiie ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
High Performance ◽  
Diffusion Method ◽  
Broth Microdilution ◽  
Serum Samples ◽  
Disk Diffusion Method ◽  
Serum Free ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Applied Dose

ABSTRACT We have evaluated the antifungal activity of micafungin in serum by using the disk diffusion method with serum-free and serum-added micafungin standard curves. Serum samples from micafungin-treated patients have been shown to exhibit adequate antifungal activity, which was in proportion to both the applied dose and the actual concentration of micafungin measured by high-performance liquid chromatography. The antifungal activity of micafungin in serum was also confirmed with the broth microdilution method.

scholarly journals Antifungal Activity of Jasminum sambac against Malassezia sp. and Non-Malassezia sp. Isolated from Human Skin Samples

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jacinta Santhanam ◽  
Farhana Nadiah Abd Ghani ◽  
Dayang Fredalina Basri
Keyword(s):  
Antifungal Activity ◽  
Essential Oil ◽  
Methanol Extract ◽  
Skin Diseases ◽  
Flowering Plant ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Inhibition Zones ◽  
Jasminum Sambac ◽  
Skin Samples

Malassezia sp. causes skin diseases such as pityriasis versicolor, folliculitis, and atopic dermatitis. The present study aims to evaluate the antifungal activity of J. sambac or Arabian jasmine, a flowering plant abundant in the Southeast Asia against Malassezia sp. using disc diffusion and broth microdilution method. The methanol extract and essential oil from the flowers and leaves of J. sambac were, respectively, prepared using solvent extraction and hydrodistillation process. Skin samples from individuals with dandruff were cultured on Sabouraud dextrose agar overlaid with olive oil. The fungi that grew were observed microscopically, tested with Tween assimilation test, and cultured on CHROMagar (the chromogenic media pioneer) to identify Malassezia sp. Out of 5 skin samples, only 2 Malassezia sp. isolates were identified based on morphology and their ability to assimilate Tween. The inhibition zones of methanol extract of flowers and leaves of J. sambac and essential oil of flowers showed potential for antifungal activity with inhibition zones of 11.10 ± 1.92, 12.90 ± 1.68, and 13.06 ± 0.26 mm, respectively, and minimum inhibitory concentration (MIC) values of 80 mg/mL to 160 mg/mL and 50%, respectively. In conclusion, J. sambac may be used as an alternative treatment against Malassezia-associated skin infections.

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