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Because of their capacity to bind metals, metal chelators are primarily employed for therapeutic purposes, but they can also find applications as colorimetric reagents and cleaning solutions as well as in soil remediation, electroplating, waste treatment, and so on. For instance, iron-chelation therapy, which is used to treat iron-overload disorders, involves removing excess iron from the blood through the use of particular molecules, like deferoxamine, that have the ability to chelate the metal. The creation of bioinspired and biodegradable chelating agents is a crucial objective that draws inspiration from natural products. In this context, starting from bioavailable molecules such as maltol and pyrogallol, new molecules have been synthetized and characterized by potentiometry, infrared spectroscopy and cyclic voltammetry. Finally, the ability of these to bind iron has been investigated, and the stability constants of ferric complexes are measured using spectrophotometry. These compounds offer intriguing scaffolds for an innovative class of versatile, multipurpose chelating agents. [ABSTRACT FROM AUTHOR]

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that stabilizes client proteins in a folded and functional state. It is composed of two identical and symmetrical subunits and each monomer consists of three domains, the N-terminal (NTD), the middle (MD), and the C-terminal domain (CTD). Since the chaperone activity requires ATP hydrolysis, molecules able to occupy the ATP-binding pocket in the NTD act as Hsp90 inhibitors, leading to client protein degradation and cell death. Therefore, human Hsp90 represents a validated target for developing new anticancer drugs. Since protozoan parasites use their Hsp90 to trigger important transitions between different stages of their life cycle, this protein also represents a profitable target in anti-parasite drug discovery. Nevertheless, the development of molecules able to selectively target the ATP-binding site of protozoan Hsp90 is challenging due to the high homology with the human Hsp90 NTD (hHsp90-NTD). In a previous work, a series of potent Hsp90 inhibitors based on a 1,4,5-trisubstituted 1,2,3-triazole scaffold was developed. The most promising inhibitor of the series, JMC31, showed potent Hsp90 binding and antiproliferative activity in NCI-H460 cells in the low-nanomolar range. In this work, we present the structural characterization of hHsp90-NTD in complex with JMC31 through X-ray crystallography. In addition, to elucidate the role of residue 112 on the ligand binding and its exploitability for the development of selective inhibitors, we investigated the crystal structures of hHsp90-NTD variants (K112R and K112A) in complex with JMC31. [ABSTRACT FROM AUTHOR]

Persisting limitations in respiratory function and gas exchange, cognitive impairment, and mental health deterioration have been observed weeks and months after acute SARS-CoV-2 (COVID-19). The present study aims at assessing the impairment at three-months in patients who successfully recovered from acute COVID-19. We collected data from May to July 2020. Patients underwent a multidimensional extensive assessment including pulmonary function test, psychological tests, thoracic echo scan, and functional exercise capacity. A total of 21 patients (M:13; Age 57.05 ± 11.02) completed the global assessment. A considerable proportion of patients showed symptoms of post-traumatic stress disorder (28.6%), moderate depressive symptoms (9.5%), and clinical insomnia (9.5%); 14.3% of patients exhibited moderate anxiety. A total of eleven patients (52.4%) showed impaired respiratory gas exchange capacity (P-DLCO, DLCO ≤ 79% pred). Compared to patients with normal gas exchange, the P-DLCO subgroup perceived a significant worsening in quality of life (QoL) after COVID-19 (p = 0.024), higher fatigue (p = 0.005), and higher impact of lung disease (p = 0.013). In P-DLCO subgroup, higher echo score was positively associated with hospitalization length of stay (p = 0.047), depressive symptoms (p = 0.042), fatigue (p = 0.035), impairment in mental health (p = 0.035), and impact of lung disease in health status (p = 0.020). Pulmonary function and echo scan lung changes were associated to worsened QoL, fatigue, and psychological distress symptoms. [ABSTRACT FROM AUTHOR]

Microwave-assisted organic synthesis (MAOS) provides a novel and efficient means of achieving heat organic reactions. Nevertheless, the potential arcing phenomena via microwave (MW) interaction with solid metal catalysts has limited its use by organic chemists. As arcing phenomena are now better understood, new applications of Pd/C-catalyzed reactions under MW dielectric heating are now possible. In this review, the state of the art, benefits, and challenges of coupling MW heating with heterogeneous Pd/C catalysis are discussed to inform organic chemists about their use with one of the most popular heterogeneous catalysts. [ABSTRACT FROM AUTHOR]

The synthesis of 2-substituted indoles starting from the corresponding unprotected 2-alkynylanilines was made possible in 3% TPGS-750-M water using Pd(OAc)2 alone as the catalyst. The reaction was sensitive to the heating mode respect to the nature of the starting material as, in many cases, convectional heating was better than microwave dielectric heating. The MW (microwave) delivery mode had also an influence in the formation of by-products and, consequently, product yields. A tandem Sonogashira-cyclisation reaction was also accomplished using Pd(OAc)2/Xphos in the nanomicellar water environment. [ABSTRACT FROM AUTHOR]