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Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

Recent estimates suggest that>300 million people are afflicted by serious fungal infections worldwide. Currentantifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of newantifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news

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Although several new antifungal drugs have been licensed in the last 5 years, some patients remain difficult to treat. The main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. In addition, some drugs penetrate poorly into sanctuary sites including eye and urine, and others are associated with considerable adverse events. Here, we review the preclinical and clinical development progress with four new antifungal agents: isavuconazole, ravuconazole,albaconazole and aminocandin.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Authors: Zhang PP, Xin XF, Xu XY, Fang LP, Wu J, Shi Y Abstract In recent years, along with the wide application of organ transplantation and immunosuppressive agents, as well as the abuse of broad spectrum antibiotics, the incidence of invasive fungal infections has been increasing gradually. The present study aimed to identify novel biomarkers in cells infected with Aspergillus fumigatus. Human umbilical vein endothelial cells (HUVECs) were infected with Aspergillus fumigatus and then harvested at different time-points (0, 1, 2, 4 and 6 h). The expression Toll-like receptor 2 (TLR2) and dectin-1 expression were e...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Friday, October 13, 2017 - 15:46Slide presentation
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Friday, October 13, 2017 - 09:24Slide presentation
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Abstract N-Myristoyltransferase (NMT) has been validated pre-clinically as a target for treatment of fungal infections. Various substituted thiochroman-4-one derivatives have been synthesized by an efficient method. The synthesized compounds 7a-y and 8a-t were evaluated for their in vitro antifungal activity against the Canidia albicans, Cryptococcus neoformans, Epidermophyton floccosum, Mucor racemosus, Microsporum gypseum and Aspergillus nigerstrain. A series of compounds exhibited significant activity (minimal inhibitory concentrotion (MIC)=0.5-16 µg/mL) against Canidia albicans and Cryptococcus ne...
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research
Tue, 10/03/2017 - 13:20News blog
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Rationale: Rationale:Invasive pulmonary aspergillosis is associated with significant morbidity and mortality in patients with liver failure. Voriconazole (VRCZ) is recommended as a primary therapeutic agent for the treatment of invasive aspergillosis and metabolized in the liver. Now, data are still lacking on the safety and appropriate dosage of VRCZ in patients with liver failure. Here, we report a representative case of invasive pulmonary fungal infection in a patient with liver failure who was treated with low-dose VRCZ. Patient concerns: Patient concerns:A 21-year-old man, presented with subacute liver failure caused...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Respiratory fungal infections are associated with high morbidity and mortality in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients, and are caused primarily by molds. Aspergillus is the most common pathogen. The net state of immunosuppression plays a major role in the risk of respiratory fungal infections after transplantation. Clinical presentation can be atypical and diagnosis can be delayed due to low sensitivity of diagnostic methods or inability to obtain adequate specimens. Fungal infections in HSCT and SOT carry a higher risk of dissemination. New prophylaxis strategies have changed the epi...
Source: Clinics in Chest Medicine - Category: Respiratory Medicine Authors: Source Type: research
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