scholarly journals A second generation fungerp analog SCY-247, shows potent in vitro activity against Candida auris and other clinically relevant fungal isolates

2020 ◽  
pp. AAC.01988-20
Author(s):  
Sherman Chu ◽  
Lisa Long ◽  
Rania Sherif ◽  
Thomas S. McCormick ◽  
Katyna Borroto-Esoda ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Second Generation ◽  
Fungal Infections ◽  
Parent Compound ◽  
Fungal Species ◽  
Antifungal Compound ◽  
Candida Auris ◽  
Fungal Cell ◽  
Antifungal Properties

Due to the increase of antifungal drug resistance and difficulties associated with drug administration, new antifungal agents for invasive fungal infections are needed. SCY-247 is a second-generation fungerp antifungal compound that interferes with the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan. We conducted an extensive antifungal screen of SCY-247 against yeast and mold strains compared with the parent compound ibrexafungerp (IBX, formerly SCY-078) to evaluate the in vitro antifungal properties of SCY-247. SCY-247 demonstrated similar activity to IBX against all of the organisms tested. Moreover, SCY-247 showed a higher percentage of fungicidal activity against the panel of yeast and mold isolates compared to IBX. Notably, SCY-247 showed considerable antifungal properties against numerous strains of Candida auris. Additionally, SCY-247 retained its antifungal activity when evaluated in the presence of synthetic urine, indicating that SCY-247 maintains activity and structural stability under environments with decreased pH levels. Finally, a time-kill study showed SCY-247 has potent anti-Candida, Aspergillus, and Scedosporium activity. In summary, SCY-247 has potent antifungal activity against various fungal species, indicating that further studies on this fungerp analog are warranted.

scholarly journals In Vitro Activity of a Novel Antifungal Compound, MYC-053, against Clinically Significant Antifungal-Resistant Strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp.

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
G. Tetz ◽  
M. Collins ◽  
D. Vikina ◽  
V. Tetz
Keyword(s):  
Cryptococcus Neoformans ◽  
Candida Glabrata ◽  
Fungal Infections ◽  
Antifungal Compound ◽  
Candida Auris ◽  
Content Type ◽  
Treatment And Prevention ◽  
Resistant Strains ◽  
Clinically Significant

ABSTRACT An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis species. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with MICs of 0.125 to 4.0 μg/ml. Notably, unlike other antifungals such as azoles, polyenes, and echinocandins, MYC-053 was effective against Pneumocystis isolates, therefore being the only synthetic antifungal that may potentially be used against Pneumocystis spp., Candida spp., and Cryptococcus spp. MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with minimal biofilm eradication concentrations equal to 1 to 4 times the MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi.

scholarly journals Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258465
Author(s):  
Mohamed Hagras ◽  
Nader S. Abutaleb ◽  
Ahmed M. Sayed ◽  
Ehab A. Salama ◽  
Mohamed N. Seleem ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Conformationally Restricted ◽  
Normal Human

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

scholarly journals In vitro activity of a novel antifungal compound, MYC-053, against clinically significant antifungal-resistant strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp

2018 ◽  
Author(s):  
G Tetz ◽  
M Collins ◽  
D Vikina ◽  
V Tetz
Keyword(s):  
Cryptococcus Neoformans ◽  
Candida Glabrata ◽  
Fungal Infections ◽  
Therapeutic Window ◽  
Antifungal Compound ◽  
Antifungal Compounds ◽  
Candida Auris ◽  
Treatment And Prevention ◽  
Resistant Strains

ABSTRACTAn urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with the minimum inhibitory concentrations (MIC) of 0.125–4.0 μg/mL. Notably, unlike other antifungal compounds, MYC-053 was effective against Pneumocystis isolates. MYC-053 was highly effective against preformed 48-h-old yeast biofilms, with the minimal biofilm eradication concentrations equal to 1–4 times MIC. The compound was not cytotoxic against L2 and A549 cell lines at concentrations over 100 μg/ml. Further, it possessed no apparent hemolytic activity up to 1000 μg/ml (the highest concentration tested). Overall, these data indicated that MYC-053 has a broad therapeutic window and may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi in neutropenic patients.

scholarly journals Hydroxytyrosol (HT) analogues act as potent antifungals by direct disruption of the fungal cell membrane

2018 ◽  
Author(s):  
George Diallinas ◽  
Nausica Rafailidou ◽  
Ioanna Kalpaktsi ◽  
Aikaterini Christina Komianou ◽  
Vivian Tsouvali ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Viral Infections ◽  
Fungal Infections ◽  
Parent Compound ◽  
Radical Scavenging ◽  
Model System ◽  
Cellular Model ◽  
Mammalian Cell Line ◽  
Fungal Cell

Fungal infections constitute an emerging threat and a prevalent health problem due to increasing number of immunocompromised people and pharmacological or other treatments aiming at viral infections, cancer or allergies. Currently used antifungals suffer from inefficiency, toxic side effects and developing drug-resistance. Additionally, over the last two decades no new classes of antifungals have been approved, emphasizing the urgent need for developing a novel generation of antifungals. Here we investigate the antifungal activity of a series of chemically synthesized Hydroxytyrosol (HT) analogues. HT is one of the major phenolic compounds in olive oil, shown to possess radical-scavenging antioxidant, antiproliferative, proapoptotic and anti-inflammatory activities. No previous report has studied HT analogues as antifungals. We show that specific analogues have broad and strong antifungal activity, significantly stronger than the parent compound HT. Using A. nidulans as an in vivo cellular model system, we show that antifungal HT analogues have an unprecedented efficiency in fungal plasma membrane destruction. Importantly, antifungal HT analogues did not show toxicity in a mammalian cell line, whereas no resistance to HT analogues was obtained by standard mutagenesis. Our results open the way for the development of a novel, efficient and safer class of antifungals.

scholarly journals Antifungal activities of quince seed mucilage hydrogel decorated with essential oils of Nigella sativa, Citrus sinensis and Cinnamon verum

2021 ◽  
Author(s):  
Mehdi Mirzaii ◽  
Marzieh Yaeghoobi ◽  
Meysam Afzali ◽  
Neginsadat Amirkhalili ◽  
Majid Mahmoodi ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Side Effects ◽  
Essential Oils ◽  
Ultrasonic Treatment ◽  
Fungal Infections ◽  
Vitro Assay ◽  
Antifungal Activities ◽  
Antifungal Properties

Background and Objectives: Candidiasis and pityriasis versicolor are opportunistic fungal infections that are caused by Candida spp. and Malassezia spp. yeasts. Conventional drugs like azole and amino derivatives are known to treat fungal skin diseases. However, drawbacks like long-term side effects and drug resistance lead to investigate on antifungal properties of phytochemicals as an alternative to available synthetic drugs. Materials and Methods: The herbal nano hydrogel was successfully synthesized from Quince Seed extract followed by ultrasonic treatment and it has been formulated using a mixture of essential oils. We evaluated the antifungal in vitro assay for a mixture of essential oils in combination with herbal nano hydrogel against Candida albicans and Malasezia furfur strains by micro dilution method. Results: The results indicated that essential oils possess antifungal activity with the MIC value of 12.5 and 6.24 mg/ml against C. albicans and M. furfur, respectively. No fungicidal effect was reported for the herbal hydrogel before nanofabrication while it shown some antifungal activity after ultrasonic treatment for 5 and 10 minutes. As anticipated; the antifungal property of essential oil mixture was appreciably improved when it combined with herbal nano hydrogel where the highest level of inhibition was observed at concentration of 3.125 mg/ml for both strains. The loss in biological activity observed when the ultrasonic treatment on herbal nano hydrogel performed for longer time. Conclusion: The proposed plant-based nano formulation shown promising in vitro antifungal activities against C. albicans and M. furfur strains and its antifungal properties were comparable with commercially available agents like clotrimazole. The new formulation expected to be safe with minimum long-term side effects. Further investigations are underway to confirm the safety and the mechanism of the action of this new herbal formulation.

scholarly journals A Glucan Synthase FKS1 Homolog inCryptococcus neoformans Is Single Copy and Encodes an Essential Function

1999 ◽  
Vol 181 (2) ◽  
pp. 444-453 ◽  
Author(s):  
John R. Thompson ◽  
Cameron M. Douglas ◽  
Weili Li ◽  
Chong K. Jue ◽  
Barnali Pramanik ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Single Copy ◽  
Fungal Species ◽  
Term Treatment ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Long Term Treatment

ABSTRACT Cryptococcal meningitis is a fungal infection, caused byCryptococcus neoformans, which is prevalent in immunocompromised patient populations. Treatment failures of this disease are emerging in the clinic, usually associated with long-term treatment with existing antifungal agents. The fungal cell wall is an attractive target for drug therapy because the syntheses of cell wall glucan and chitin are processes that are absent in mammalian cells. Echinocandins comprise a class of lipopeptide compounds known to inhibit 1,3-β-glucan synthesis, and at least two compounds belonging to this class are currently in clinical trials as therapy for life-threatening fungal infections. Studies ofSaccharomyces cerevisiae and Candida albicansmutants identify the membrane-spanning subunit of glucan synthase, encoded by the FKS genes, as the molecular target of echinocandins. In vitro, the echinocandins show potent antifungal activity against Candida and Aspergillusspecies but are much less potent against C. neoformans. In order to examine why C. neoformans cells are less susceptible to echinocandin treatment, we have cloned a homolog of S. cerevisiae FKS1 from C. neoformans. We have developed a generalized method to evaluate the essentiality of genes inCryptococcus and applied it to the FKS1 gene. The method relies on homologous integrative transformation with a plasmid that can integrate in two orientations, only one of which will disrupt the target gene function. The results of this analysis suggest that the C. neoformans FKS1 gene is essential for viability. The C. neoformans FKS1 sequence is closely related to the FKS1 sequences from other fungal species and appears to be single copy in C. neoformans. Furthermore, amino acid residues known to be critical for echinocandin susceptibility in Saccharomyces are conserved in theC. neoformans FKS1 sequence.

scholarly journals In VitroScreening of 10 Edible Thai Plants for Potential Antifungal Properties

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Supattra Suwanmanee ◽  
Thitinan Kitisin ◽  
Natthanej Luplertlop
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
Psidium Guajava ◽  
Antifungal Drugs ◽  
Hot Water ◽  
Human Skin Fibroblast ◽  
Zone Of Inhibition ◽  
Antifungal Properties ◽  
Crude Extracts

Growing rates of fungal infections and increasing resistance against standard antifungal drugs can cause serious health problems. There is, therefore, increasing interest in the potential use of medicinal plants as novel antifungal agents. This study investigates the antifungal properties of crude plant extracts from ten medicinal plant species. Crude samples were extracted using the hot water extraction process. The minimum inhibitory concentrations (MIC) and diameter zone of inhibition were determined in each extract against ten fungal strains, and fluconazole was used as a positive control. The cytotoxicity of crude extracts onin vitrohuman skin fibroblast (HSF) cell models was determined by MTT assay. Of the ten crude extracts,Psidium guajavaL. exhibited the highest antifungal activity, diameter zone of inhibition, and percentage HSF cell viability. Although all extracts exhibited antifungal activity,Psidium guajava L. had the greatest potential for developing antifungal treatments.

Antifungal Proteins from Plant Latex

2020 ◽  
Vol 21 (5) ◽  
pp. 497-506
Author(s):  
Mayck Silva Barbosa ◽  
Bruna da Silva Souza ◽  
Ana Clara Silva Sales ◽  
Jhoana D’arc Lopes de Sousa ◽  
Francisca Dayane Soares da Silva ◽  
...  
Keyword(s):  
Cell Walls ◽  
Defense Mechanisms ◽  
Hydrolytic Enzymes ◽  
Fungal Species ◽  
Biologically Active ◽  
Protein Classification ◽  
Fungal Cell ◽  
Antifungal Proteins ◽  
Plant Latex

Latex, a milky fluid found in several plants, is widely used for many purposes, and its proteins have been investigated by researchers. Many studies have shown that latex produced by some plant species is a natural source of biologically active compounds, and many of the hydrolytic enzymes are related to health benefits. Research on the characterization and industrial and pharmaceutical utility of latex has progressed in recent years. Latex proteins are associated with plants’ defense mechanisms, against attacks by fungi. In this respect, there are several biotechnological applications of antifungal proteins. Some findings reveal that antifungal proteins inhibit fungi by interrupting the synthesis of fungal cell walls or rupturing the membrane. Moreover, both phytopathogenic and clinical fungal strains are susceptible to latex proteins. The present review describes some important features of proteins isolated from plant latex which presented in vitro antifungal activities: protein classification, function, molecular weight, isoelectric point, as well as the fungal species that are inhibited by them. We also discuss their mechanisms of action.

Smart Gn-Keto Nanohybrid Embedded Topical System for Effective Management of Dermatophytosis

2019 ◽  
Vol 9 (1) ◽  
pp. 21-28
Author(s):  
Nisha Sharma ◽  
Shashikiran Misra
Keyword(s):  
Antifungal Activity ◽  
Fungal Infections ◽  
High Surface ◽  
High Surface Area ◽  
Vital Role ◽  
Common Disease ◽  
Microdilution Method ◽  
Enhanced Solubility ◽  
Bioactive Agents

Background and Objectives: Dermatophytosis (topical fungal infection) is the 4th common disease in the last decade, affecting 20-25% world’s population. Patients of AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to dermatophytosis. The conventional topical dosage proves effective as prophylactic in preliminary stage. In the advanced stage, the therapeutics interacts with healthy tissues before reaching the pathogen site, showing undesirable effects, thus resulting in pitiable patient compliance. The youngest carbon nano-trope “Graphene” is recently used to manipulate bioactive agents for therapeutic purposes. Here, we explore graphene via smart engineering by virtue of high surface area and high payload for therapeutics and developed graphene–ketoconazole nanohybrid (Gn-keto) for potent efficacy towards dermatophytes in a controlled manner. </P><P> Methods: Polymethacrylate derivative Eudragit (ERL100 and ERS 100) microspheres embedded with keto and Gn-keto nanohybrid were formulated and characterized through FTIR, TGA, and SEM. In vitro drug release and antifungal activity of formulated Gn-keto microspheres were assessed for controlled release and better efficacy against selected dermatophytes. </P><P> Results: Presence of numerous pores within the surface of ERL100 microspheres advocated enhanced solubility and diffusion at the site of action. Controlled diffusion across the dialysis membrane was observed with ERS100 microspheres owing to the nonporous surface and poor permeability. Antifungal activity against T. rubrum and M. canis using microdilution method focused on a preeminent activity (99.785 % growth inhibition) of developed nanohybrid loaded microspheres as compared to 80.876% of keto loaded microspheres for T. rubrum. The culture of M. canis was found to be less susceptible to formulated microspheres. Conclusion: Synergistic antifungal activity was achieved by nanohybrid Gn-Keto loaded microspheres against selected topical fungal infections suggesting a vital role of graphene towards fungi.

Synthesis and Biological Activity of 3-(substitutedphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine: Part II

2020 ◽  
Vol 18 ◽  
Author(s):  
Niranjan Kaushik ◽  
Nitin Kumar ◽  
Anoop Kumar ◽  
Vikas Sharma
Keyword(s):  
Antifungal Activity ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Mass Spectral Data ◽  
Triazole Derivatives ◽  
Mass Spectral ◽  
Fungal Strains ◽  
Antifungal Properties ◽  
Antifungal Potential ◽  
Spectral Data Analysis

Background: Fungal infections are opportunistic infections that become a serious problem to human health. Objective: Considering the antifungal potential of triazole nucleus, the study was carried out with the objective to synthesize some novel triazole derivatives with antifungal potential. Method: 1,2,4-triazole derivatives were synthesized via a two step reaction (reported earlier). The first step involves reaction of substituted benzoic acid with thiocarbohydrazide to form 4-amino-3-(substituted phenyl)-5-mercapto-1, 2, 4-triazole derivatives (1a-1k) while in second step, synthesized compounds (1a-1k) were then subsequently treated with substituted acetophenone to yield substituted (4-methoxyphenyl-7H-[1, 2, 4] triazolo [3, 4-b][1,3,4] thiadiazine derivatives (2a-2k). All synthesized compounds were characterized by IR, 1H NMR, and Mass spectral data analysis and were screened for their antifungal properties against different fungal strains i.e. Candida tropicalis (ATCC-13803, ATCC-20913), Candida albicans (ATCC-60193), Candida inconspicua (ATCC-16783) and Candida glabrata (ATCC-90030, ATCC-2001). Results: Compound 2d displayed better percentage inhibition (26.29%, 24.81%) than fluconazole (24.44%, 22.96%) against ATCC-16783, ATCC-2001 fungal strains respectively at 100µg/ml. Compound 2f also displayed better percentage inhibition (28.51%) against ATCC-90030 as compared to fluconazone (27.4%) at 200 µg/ml. Similarly, compounds 2e and 2j also exhibited better antifungal properties than fluconazole at 200µg/ml. Compound 2e was found most potent against ATCC13803 (30.37%) and ATCC-90030 (30.37%) fungal strains as compared to fluconazole (28.14%, 27.4%) at 200 µg/ml respectively whereas compound 2j exhibited better antifungal activity (28.51%) against ATCC-60193 than fluconazole (27.7%) at 200 µg/ml. Conclusion: The results were in accordance with our assertions for triazole derivatives, as all compounds displayed moderate to good antifungal activity.

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