The Celecoxib Derivative AR-12 Has Broad-Spectrum Antifungal Activity In Vitro and Improves the Activity of Fluconazole in a Murine Model of Cryptococcosis.

Only one new class of antifungal drugs has been introduced into clinical practice in the last 30 years, and thus the identification of small molecules with novel mechanisms of action is an important goal of current anti-infective research. Here, we describe the characterization of the spectrum of in vitro activity and in vivo activity of AR-12, a celecoxib derivative which has been tested in a phase I clinical trial as an anticancer agent. AR-12 inhibits fungal acetyl coenzyme A (acetyl-CoA) synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news

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Conclusion and Perspectives CYP51 plays a crucial role in fungal invasive growth, hyphae formation and virulence, and inhibitors targeting CYP51 have always been an important component of antifungal agents. Further researches on fungal CYP51s might set about from the following aspects: First, while the detailed crystal structures of several susceptible pathogenic fungi CYP51 have been elaborated, those of drug-resistant variants are still in hypothesis. If those structures were elucidated, targeting at common drug-resistant CYP51 protein variants could probably be promising. Second, it deserves more in-depth researches to...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study they also showed PTX3 localized in NETs formed after neutrophil activation (5). Proteomics analysis revealed that PTX3 forms complexes with two anti-microbial proteins [azurocidin (AZU1) and myeloperoxidase (MPO)] associated to NETs (30). More recently, PTX3 localization in NETs has been confirmed, and the colocalization with AZU1 and MPO has been defined more accurately (31). Further investigation will be needed to understand the involvement of PTX3 interaction with AZU1 and MPO in their antibacterial role during NET formation. Regulation of Complement Activation PTX3 interaction with microorganisms is not...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion In conclusion, F. keratoplasticum and F. petroliphilum were the most frequent species in this study. Amphotericin B showed lower MICs against Fusarium species whereas the antifungal azoles and the fungicide difenoconazole exhibited higher MICs against FSSC. Ethics Statement Samples were collected during routine patient care and the study was retrospective, therefore it was determined by the local Institutional Review Board of the Hospital de Clínicas, Federal University of Paraná and CAPES that ethical clearance was not indicated. Author Contributions PH, AA-H, FQ-T, and JM designed the study....
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
AbstractThere have been conflicting reports of false positive galactomannan assay results in patients with systemic cryptococcosis. We sought to determine the frequency of GM positivity in patients with pulmonary cryptococcosis and confirm the source of this cross-reactivity in vitro. We conducted a retrospective study to elucidate the rate of galactomannan (GM) false positivity and cause in a cohort of 29 patients with pulmonary cryptococcal disease. The production of GM cross-reacting substances by clinical isolates and laboratory isolates ofC. neoformans was tested in vitro. The mean serum GM index (PlateliaAspergillus)...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
CONCLUSION: Mold infection tended to develop in patients with active lupus disease with high mortality. Co-infection is not rare. Lymphopenia and an accumulated dose of glucocorticoid are associated with invasive fungal disease in lupus patients. PMID: 30526329 [PubMed - as supplied by publisher]
Source: Lupus - Category: Rheumatology Authors: Tags: Lupus Source Type: research
Conclusion: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.
Source: Indian Journal of Medical Microbiology - Category: Microbiology Authors: Source Type: research
In this study, we analyzed the cytotoxicity, immunosuppressive activity, and antifungal activity of four FK506 analogs, 31-O-demethyl-FK506, 9-deoxo-FK506, 9-deoxo-31-O-demethyl-FK506, and 9-deoxo-prolyl-FK506, in comparison with FK506. The four FK506 analogs generally possess lower cytotoxicity and immunosuppressive activity than FK506. The FK506 analogs, except for 9-deoxo-prolyl FK506, have strong antifungal activity against Cryptococcus neoformans and Candida albicans, which are two major invasive pathogenic yeasts, due to the inhibition of the calcineurin pathway. Furthermore, the FK506 analogs, except for 9-deoxo-pro...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
LITFL • Life in the Fast Lane Medical Blog LITFL • Life in the Fast Lane Medical Blog - Emergency medicine and critical care medical education blog aka Tropical Travel Trouble 009 The diagnosis of HIV is no longer fatal and the term AIDS is becoming less frequent. In many countries, people with HIV are living longer than those with diabetes. This post will hopefully teach the basics of a complex disease and demystify some of the potential diseases you need to consider in those who are severely immunosuppressed. While trying to be comprehensive this post can not be exhaustive (as you can imagine any patient with ...
Source: Life in the Fast Lane - Category: Emergency Medicine Authors: Tags: Clinical Cases Tropical Medicine AIDS art cryptococcoma cryptococcus HIV HIV1 HIV2 PEP PrEP TB toxoplasma tuberculoma Source Type: blogs
QIDP Designation Granted for Treatment of Cryptococcosis Provides Priority Review, Fast-Track Status and Five Additional Years of Market Exclusivity SAN DIEGO, March 19, 2018 -- (Healthcare Sales &Marketing Network) -- Amplyx Pharmaceuticals, a compan... Biopharmaceuticals, FDA Amplyx Pharmaceuticals, Candida, Aspergillus
Source: HSMN NewsFeed - Category: Pharmaceuticals Source Type: news
Conclusions: Frequency of infection in APAP cases were similar to the previous report. Infection might improve or deteriorate the clinical course of APAP.Financial support: This study was partially granted from AMED; DLD/14526278 to Y. Inoue and T. Arai and PAP/14526182 to Y. Inoue.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Diffuse Parenchymal Lung Disease Source Type: research
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