New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease MPro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies.

New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.

A facile synthesis of CeO2 from the GO@Ce-MOF precursor and its efficient performance in the oxygen evolution reaction.

Electrochemical water splitting has enticed fascinating consideration as a key conduit for the advancement of renewable energy systems. Fabricating adequate electrocatalysts for water splitting is fervently preferred to curtail their overpotentials and hasten practical utilizations. In this work, a series of Ce-MOF, GO@Ce-MOF, calcinated Ce-MOF, and calcinated GO@Ce-MOF were synthesized and used as high-proficient electrocatalysts for the oxygen evolution reaction. The physicochemical characteristics of the prepared samples were measured by diverse analytical techniques including SEM, HRTEM, FTIR, BET, XPS, XRD, and EDX. All materials underwent cyclic voltammetry tests and were evaluated by electrochemical impedance spectroscopy and oxygen evolution reaction. Ce-MOF, GO@Ce-MOF, calcinated Ce-MOF, and calcinated GO@Ce-MOF have remarkable properties such as enhanced specific surface area, improved catalytic performance, and outstanding permanency in the alkaline solution (KOH). These factors upsurge ECSA and intensify the OER performance of the prepared materials. More exposed surface active-sites present in calcinated GO@Ce-MOF could be the logic for superior electrocatalytic activity. Chronoamperometry of the catalyst for 15°h divulges long-term stability of Ce-MOF during OER. Impedance measurements indicate higher conductivity of synthesized catalysts, facilitating the charge transfer reaction during electrochemical water splitting. This study will open up a new itinerary for conspiring highly ordered MOF-based surface active resources for distinct electrochemical energy applications.

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort.

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones.

The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms.

New barbiturates and thiobarbiturates as potential enzyme inhibitors.

A series of 27 new barbiturates and thiobarbiturates have been synthesized by a convenient multi-component reaction in overall excellent yields (87-96%). All the synthesized compounds were characterized by 1H, 13C NMR, EIMS and elemental analysis (C, H, N and S). Furthermore, all compounds were screened for in vitro antioxidant (DPPH radical scavenging), lipoxygenase, chymotrypsin, α-glucosidase and anti-urease activities. Out of the series, 23 in DPPH, 14 in lipoxygenase, 2 in chymotrypsin have shown appreciable IC50 values.

(±)-4,12,15,18,26-Penta-hydroxy-13,17-dioxahepta-cyclo-[14.10.0.0.0.0.0.0]hexa-cosa-1,3(14),6(11),7,9,15,19,21,23-nona-ene-5,25-dione monohydrate.

The title compound, C(24)H(14)O(9)·H(2)O, displays a cup-shaped form. The water mol-ecule is disordered over two set of sites with an occupancy ratio of 0.78:0.22. The mol-ecule of the compound has four stereocenters and corresponds to the SSRR/RRSS diastereoisomer. In the mol-ecule, the maximum dihedral angle between the planar benzene rings is 80.40 (4)°. The H atoms of the hy-droxy groups are engaged in hydrogen bonding, forming infinite chains parallel to the a axis. These chains are inter-linked through water mol-ecules, resulting in the formation of a two-dimensional network parallel to the (001) plane. Futhermore C-H⋯O, C-H⋯π and slipped π-π inter-actions result in the formation of a three-dimensional network.

CCL18 in peritoneal dialysis patients and encapsulating peritoneal sclerosis.

BACKGROUND: Peritoneal fibrosis manifests clinically as membrane failure or encapsulating peritoneal sclerosis (EPS). There are no clinical or biochemical tests to determine the rate of progression of peritoneal fibrosis. CCL18/pulmonary and activation-regulated chemokine (PARC) is profibrotic and stimulates collagen production independent of the effect of transforming growth factor beta. This has not been studied in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: We have prospectively studied 106 patients, free from infection/recent peritonitis. A high concentration of CCL18 was discovered by multiplex antibody arrays and quantified by ELISA. Serum and dialysate levels were examined for their prognostic values. RESULTS: By multiple regression analysis, dialysate CCL18 (6·76 ± 0·66 µg 4 h⁻¹) correlated with increasing membrane transport status (TS) (P < 0·0001) and total glucose exposure/24 h (P = 0·033). Serum CCL18 correlated with high TS (P = 0·0001) and duration of PD (P = 0·001). After 12 months of follow-up, 57 patients remained on PD while 12 patients were transferred to haemodialysis (HD) and seven developed EPS. Patients who subsequently developed EPS had higher baseline dialysate CCL18 (11·5 ± 3·6 µg 4 h⁻¹ vs. 5·6 ± 0·82 µg 4 h⁻¹, P = 0·03) and serum CCL18 (156·9 ± 12·8 ng mL⁻¹ vs. 124·8 ± 12·2 ng mL⁻¹, P = 0·02) compared with the stable PD group. CONCLUSION: This is the first report of high levels of CCL18 in the spent dialysate and serum from long-term PD patients. These levels correlated with dysfunction of peritoneal membrane transport status, therefore following CCL18 in a longitudinal study may be of interest.

4-{2-[(Z)-(5-Methyl-2-fur-yl)methyl-idene-amino]-eth-yl}benzene-sulfonamide.

In the title compound, C(14)H(16)N(2)O(3)S, the dihedral angle between the phenyl and 5-methyl-furan groups is 54.89 (14)° and the C=N bond assumes a trans conformation. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) ring motifs. The dimers are inter-linked by N-H⋯N hydrogen bonds, resulting in the formation of infinite chains extending along the b axis. The packing is consolidated by weak C-H⋯π inter-actions.

[5-(2-Fur-yl)-6-nitro-1,2,3,5,6,7-hexa-hydro-imidazo[1,2-a]pyridin-8-yl](phen-yl)methanone.

In the title compound, C(18)H(17)N(3)O(4), the furyl and phenyl rings are inclined at almost right angles [85.77 (7) and 63.25 (7)°, respectively] to the central imidazo[1,2-a]pyridinyl unit. The structure displays both inter- and intra-molecular N-H⋯O hydrogen bonding.

(4-Fluoro-phen-yl)[6-(2-fur-yl)-7-nitro-2,3,4,6,7,8-hexa-hydro-1H-pyrido[1,2-a]pyrimidin-9-yl]methanone.

In the title compound, C(19)H(18)FN(3)O(4), the fused pyridine and pyrimidine rings adopt half-chair conformations. The structure displays intra-molecular N-H⋯O and inter-molecular N-H⋯F hydrogen bonding.