Cysteine protease inhibitors: from evolutionary relationships to modern chemotherapeutic design for the treatment of infectious diseases

Cysteine proteases are one of the largest groups of proteases and are involved in many important biological functions in all kingdoms of life. They are virulence factors of a range of eukaryotic, bacterial and viral pathogens and are involved in host invasion, pathogen replication and disruption of the host immune response. Their activity is regulated by a range of protease inhibitors. This review discusses the various families of cysteine protease inhibitors, their different modes of inhibition and their evolutionary relationships. These inhibitors as well as the recent discovery of propeptide and propeptide-like inhibitors provide insights into the structures that are important for particular inhibitory mechanisms, thus forming the foundation for the design of future therapeutics.     

Crystal growth, structures, and optical properties of the cubic double perovskites Ba2MgWO6 and Ba2ZnWO6

Single crystals of the tungstates Ba₂MgWO₆ and Ba₂ZnWO₆ have been grown for the first time. The crystals were prepared with molten potassium carbonate acting as a flux. According to the single-crystal X-ray diffraction structure determination, the compounds crystallize in space group Fm3¯m of the cubic system with a double perovskite structure, A₂BB′O₆. These structural findings were confirmed with neutron diffraction on polycrystalline samples synthesized by a high-temperature solid-state route. Both sets of diffraction data reveal that the M²⁺ and W⁶⁺ cations are fully ordered on the B and B′ sites. Ba₂MgWO₆ and Ba₂ZnWO₆ exhibit room-temperature luminescence with green and yellow emissions, respectively.     

Magnetic‐Structure‐Stabilized Polarization in an Above‐Room‐Temperature Ferrimagnet

Above‐room‐temperature polar magnets are of interest due to their practical applications in spintronics. Here we present a strategy to design high‐temperature polar magnetic oxides in the corundum‐derived A₂BB′O₆ family, exemplified by the non‐centrosymmetric (R3) Ni₃TeO₆‐type Mn²⁺₂Fe³⁺Mo⁵⁺O₆, which shows strong ferrimagnetic ordering with T_C=337 K and demonstrates structural polarization without any ions with (n?1)d¹⁰ns⁰, d⁰, or stereoactive lone‐pair electrons. Density functional theory calculations confirm the experimental results and suggest that the energy of the magnetically ordered structure, based on the Ni₃TeO₆ prototype, is significantly lower than that of any related structure, and accounts for the spontaneous polarization (68 μC cm^?2) and non‐centrosymmetry confirmed directly by second harmonic generation. These results motivate new directions in the search for practical magnetoelectric/multiferroic materials.     

Effect of Zn substitution on the magnetic properties of Mg1−xZnxFe2O4 ferrites

Polycrystalline Mg_1−xZn_xFe₂O₄ (x=0.0–0.6) ferrites have been prepared using solid-state reaction technique. The X-ray diffraction analysis revealed that the samples crystallize in a single-phase cubic spinel structure. The lattice parameter increases linearly with increase in zinc content obeying Vegard's law. The continuous decrease in Curie temperature (T_c) with an increase in Zn content is attributed to the weakening of A–B exchange interaction. Saturation magnetization (M_s) and magnetic moment are observed to increase up to x=0.4, and thereafter decrease due to the spin canting in B-sites. The initial permeability is found to increase with the addition of Zn²⁺ ions but the resonance frequency shifts towards the lower frequency.     

Boosting Solid‐State Diffusivity and Conductivity in Lithium Superionic Argyrodites by Halide Substitution

Developing high‐performance all‐solid‐state batteries is contingent on finding solid electrolyte materials with high ionic conductivity and ductility. Here we report new halide‐rich solid solution phases in the argyrodite Li₆PS₅Cl family, Li_6?xPS_5?xCl_1+x, and combine electrochemical impedance spectroscopy, neutron diffraction, and ⁷Li NMR MAS and PFG spectroscopy to show that increasing the Cl^?/S^2? ratio has a systematic, and remarkable impact on Li‐ion diffusivity in the lattice. The phase at the limit of the solid solution regime, Li_5.5PS_4.5Cl_1.5, exhibits a cold‐pressed conductivity of 9.4±0.1 mS cm^?1 at 298 K (and 12.0±0.2 mS cm^?1 on sintering)—almost four‐fold greater than Li₆PS₅Cl under identical processing conditions and comparable to metastable superionic Li₇P₃S₁₁. Weakened interactions between the mobile Li‐ions and surrounding framework anions incurred by substitution of divalent S^2? for monovalent Cl^? play a major role in enhancing Li⁺‐ion diffusivity, along with increased site disorder and a higher lithium vacancy population.     

Deviations from ideality in mixtures of two ionic liquids containing a common ion

Excess molar volumes of six binary mixtures composed of two ionic liquids of the 1-methyl-3-alkyl-imidazolium bis(trifluoromethylsulfonyl)amide family -- ([C(m)()mim] + [C(n)()mim])[NTf(2)] with n and m ranging from 2 to 10 -- were measured for several compositions at 298 and 333 K. Similarly, three other binary systems containing [C(4)mim](+) (1-methyl-3-butylimidazolium) as a common cation have been studied: [C(4)mim]([NTf(2)] + [PF(6)]), [C(4)mim]([NTf(2)] + [BF(4)]) and [C(4)mim]([BF(4)] + [PF(6)]). Thus, the mixing process of two distinct ions of equal sign embedded in a constant field network of a given counterion was analyzed. All systems exhibit small, positive V(E) values of the order of a few tenths of cm(3) mol(-1), which are essentially temperature and pressure independent. The results show additive trends, for instance, the V(E) values become larger as the difference between the alkyl chain lengths of the two cations increases. The Flory theory of mixtures provides a useful, semiquantitative correlation between the excess volumes and excess enthalpies in these systems, allowing for comparison with analogous results obtained within the linear primary alcohols.     

Green Synthesis of Oxoquinoline-1(2H)-Carboxamide as Antiproliferative and Antioxidant Agents: An Experimental and In-Silico Approach to High Altitude Related Disorders

At high altitudes, drops in oxygen concentration result in the creation of reactive oxygen and nitrogen species (RONS), which cause a variety of health concerns. We addressed these health concerns and reported the synthesis, characterization, and biological activities of a series of 10 oxoquinolines. N-Aryl-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)carboxamides (5a–j) were accessed in two steps under ultrasonicated irradiation, as per the reported method. The anticancer activity was tested at 10 µM against a total of 5 dozen cancer cell lines obtained from nine distinct panels, as per the National Cancer Institute (NCI US) protocol. The compounds 5a (TK-10 (renal cancer); %GI = 82.90) and 5j (CCRF-CEM (Leukemia); %GI = 58.61) showed the most promising anticancer activity. Compound 5a also demonstrated promising DPPH free radical scavenging activity with an IC₅₀ value of 14.16 ± 0.42 µM. The epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), two prospective cancer inhibitor targets, were used in the molecular docking studies. Molecular docking studies of ligand 5a (docking score = −8.839) against the active site of EGFR revealed two H-bond interactions with the residues Asp855 and Thr854, whereas ligand 5a (docking = −5.337) interacted with three H-bond with the residues Gln92, Gln67, and Thr200 against the active site CA. The reported compounds exhibited significant anticancer and antioxidant activities, as well as displayed significant inhibition against cancer targets, EGFR and CA, in the molecular docking studies. The current discovery may aid in the development of novel compounds for the treatment of cancer and oxidative stress, and other high altitude-related disorders.     

6,7‐Dihydrodibenzo[e,g]azulen‐8(5H)‐one and 12,13‐dihydrobenzo[e]­napth­[2,1‐g]­azulen‐14(11H)‐one

In the structures of the title compounds, 6,7‐di­hydro­dibenzo[e,g]­azulen‐8(5H)‐one, C₁₈H₁₄O, (I), and 12,13‐di­hydro­benzo[e]­napth­[2,1‐g]­azulen‐14(11H)‐one, C₂₂H₁₆O, (II), the azulene group is in a boat‐envelope conformation. The structures are stabilized by weak C—H?O interactions.     

The determination of magnetic anisotropy constants from torque curves

The procedures by which magnetic anisotropy constants are evaluated from torque curves are examined with reference to some calculated torque curves for an ideal uniaxial crystal. The results are compared with some torque measurements on a crystal of cobalt.     

A dianionic oxy-cope rearrangement route to benzotropones - part XII

The divinyl carbinols $\text{3}$ and $\text{6}$ furnished the benzotropones $\text{4}$ and $\text{7}$ respectively, when treated with base.