Synthesis and antifungal activity of novel oxazolidin-2-one linked-1,2,3-triazole derivatives

Artículo IndizadoNovel oxazolidin-2-one-linked 1,2,3-triazole derivatives (4a–k) were synthesized by straightforward and versatile azide–enolate (3 + 2) cycloaddition. The series of compounds was screened for antifungal activity against four filamentous fungi as well as six yeast species of Candida spp. According to their efficiency and breadth of scope, they can be ordered as 4k > 4d > 4h > 4a, especially in relation to the activity displayed against Candida glabrata ATCC-34138, Trichosporon cutaneum ATCC-28592 and Mucor hiemalis ATCC-8690, i.e. compounds 4d, 4h and 4k showed excellent activity against C. glabrata (MIC 0.12, 0.25 and 0.12 μg mL−1, respectively), better than that of itraconazole (MIC 1 μg ml−1). The activity of compound 4d (MIC = 2 μg mL− 1) was higher than that observed for the standard antifungal drug (MIC = 8 μg mL−1) against Trichosporon cutaneum, while compound 4k displayed an excellent antimycotic activity against Mucor hiemalis (MIC = 2 μg mL−1 vs. 4 μg mL−1 for itraconazole). In addition, we describe herein a novel mild and eco-friendly synthetic protocol for obtaining β-ketosulfones (adducts to afford compounds 4a–k) from α-brominated carbonyls in an aqueous nanomicellar medium at room temperature.CONACYT, Secretaría de Investigación de Estudios Avanzados de la UAE

Vanadium Inhalation in a Mouse Model for the Understanding of Air-Suspended Particle Systemic Repercussion

There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature

Covalent Chemistry on a Van Der Waals Heterostructure

The building of van der Waals heterostructures and the decoration of 2D materials with organic molecules share a common goal: to obtain ultrathin materials with tailored properties. Performing controlled chemistry on van der Waals heterostructures would add an extra level of complexity, providing a pathway towards 2D‑2D-0D mixed-dimensional heterostructures. Here we show that thiol-ene-like “click” chemistry can be used to decorate franckeite, a naturally occurring van der Waals heterostructure with maleimide reagents. ATR-IR and NMR analyses corroborate the Michael addition mechanism via the formation of a S–C covalent bond, while Raman and HR-TEM show that the SnS2-PbS alternating structure of franckeite is preserved, and suggest that SnS2 reacts preferentially, which is confirmed through XPS. We illustrate how this methodology can be used to add functional molecular moieties by decorating franckeite with porphyrins. UV-vis-NIR spectroscopy confirms that the chromophore ground state remains operative, showing negligible ground-state interactions with the franckeite. Excited-state interactions across the hybrid interface are revealed. Time-resolved photoluminescence confirms the presence of excited-state de-activation in the linked porphyrin ascribed to energy transfer to the franckeite.</p

Persistent high disease activity in the anticarbamylated protein antibody positive early arthritis patients independently of treatment

Background: There is great interest in the identification of prognostic biomarkers informing early therapeutic decisions for the improvement of rheumatoid arthritis (RA) evolution. Promising results in early arthritis (EA) patients indicate the anti-carbamylated protein antibodies (ACarPA) may serve this function. In effect, they are associated with high baseline disease activity and, in our patients, with less improvement in the first 6-months of follow-up. This association was independent of sex, age at diagnosis, time since symptoms onset, smoking and the year of onset. However, the influence of the treatment has not been explored yet. Objectives: We aimed to explore the influence of the initial treatment on the persistent high disease activity associated with the presence of ACarPA in EA patients. Methods: Samples were obtained at the first visit of two EA cohorts from Hospital Universitario La Paz and Hospital Universitario La Princesa, which recruit patients within one year from the clinical onset. Information on the initial treatment and the disease activity at the baseline and at 6-months of follow-up was available from 546 patients. Treatment was categorized according to the use of corticosteroids, methotrexate (MTX) and other DMARDs, and considering changes in the first 6 months. In addition, MTX dose was considered either quantitatively or as a dichotomous variable (? 12.5 mg and < 12.5 mg). Main effects general linear regression was used for analysis, including the treatment and the other confounders as covariates. Results: A large fraction (83%) of the EA patients received specific treatment from the initial visit. It comprised DMARD (50.1%), corticosteroids (10.6%), or a combination of both (39.3%). The most common DMARD was MTX (82.2%), whereas less frequently used medications included sulfasalazine (5.4%), leflunomide (3.2%), hydroxychloroquine (8.1%) and other (1.0%). The 35.5% of the treated patients maintained the treatment during the 6-month follow-up. The presence of ACarPA was associated with a 0.45 higher mean baseline DAS28 and with less decrease of DAS28 (?DAS28) from the baseline to 6 months of follow-up (? = 0.08, p = 0.016), as already communicated. This latter association persisted without modification after accounting for the initial treatment (DMARD, corticosteroids, and changes in treatment). In addition, it was independent of the consideration of all DMARDs in a single group, or separated into two categories: MTX and the other. Similarly, the association was independent on MTX dose, defined both as a categorical or a quantitative variable. Conclusion: The association of ACarPA with a persistently increased disease activity in EA patients is independent of the initial treatment. These results reinforce the possibility that ACarPA can be useful as prognostic biomarkers for the first 6 months of evolution and indicate the need for personalized management of the patients carrying ACarPA

Value of antibodies against acetylated peptides for the classification of patients with early arthritis

Methods: A total of 438 patients with available samples and information were randomly selected from two early arthritis clinics. The AAPA were determined in baseline sera as previously described (1). Two peptides were included, one acetylated at a lysine (anti-AcLys) and the other at an ornithine (anti-AcOrn) and considered either individually or combined. The sensitivity, specificity, predictive positive (PPV) and negative (PNV) values and the AUC of the ROC curve were assessed. Logistic regression was also applied adjusting for age, sex, the centre of origin, anti-CCP, and RF. The study was approved by the ethics committee of the Hospital Universitario La Paz, the Hospital Universitario La Princesa, and Auton?mico de Galicia. Results: The AAPA at baseline were sensitive and specific for the classification of the patients fulfilling RA criteria (46.8%) at the end of the 2-year follow-up (table 1). Specifically, the anti-AcOrn antibodies were slightly more sensitive and specific than the anti-AcLys ones. The two and their combination showed a conserved specificity for the seronegative patients, but a lower sensitivity than for the seropositive ones. Consequently, the PPV for the seronegative patients was low, although the NPV was high. In the same vein, the AUC was insufficient for the seronegative patients. The regression analysis including the anti-CCP and RF revealed a significant contribution of the anti-AcOrn antibodies (OR = 2.1, 95% CI = 1.1 ? 4.0, P = 0.02), but not of the anti-AcLys antibodies. On the other hand, the inclusion of the AAPA in the classification resulted in an increase in sensitivity of 5.4% at the cost of a 13.7% lower specificity, which is an improvement over the anti-carbamylated protein antibodies. Conclusion: The AAPA show high specificity and sensitivity for RA in early arthritis patients. However, their contribution to RA classification is minor once RF and the anti-CCP antibodies have been considered. But nevertheless, AAPA supports the drive to close the diagnostic gap in this early disease phase and to increase the likelihood of successful therapy