Exploring naphthyl derivatives as SARS-CoV papain-like protease (PLpro) inhibitors and its implications in COVID-19 drug discovery

Molecular Diversity - Novel coronavirus disease 2019 (COVID-19) emerges as a serious threat to public health globally. The rapid spreading of COVID-19, caused by severe acute respiratory syndrome...     

A modified fractional least mean square algorithm for chaotic and nonstationary time series prediction

A method of modifying the architecture of fractional least mean square （FLMS） algorithm is presented to work with nonlinear time series prediction. Here we incorporate an adjustable gain parameter in the weight adaptation equation of the original FLMS algorithm and absorb the gamma function in the fractional step size parameter. This approach provides an interesting achievement in the performance of the filter in terms of handling the nonlinear problems with less computational burden by avoiding the evaluation of complex gamma function. We call this new algorithm as the modified fractional least mean square （MFLMS） algorithm. The predictive performance for the nonlinear Mackey glass chaotic time series is observed and evaluated using the classical LMS, FLMS, kernel LMS, and proposed MFLMS adaptive filters. The simulation results for the time series with and without noise confirm the superiority and improvement in the prediction capability of the proposed MFLMS predictor over its counterparts.     

Solution-State 2D NMR Spectroscopy of Mixtures HyperpolarizedUsing Optically Polarized Crystals

The HYPNOESYS method (Hyperpolarized NOE System), which relies on the dissolution of optically polarized crystals, has recently emerged as a promising approach to enhance the sensitivity of NMR spectroscopy in the solution state. However, HYPNOESYS is a single-shot method that is not generally compatible with multidimensional NMR. Here we show that 2D NMR spectra can be obtained from HYPNOESYS-polarized samples, using single-scan acquisition methods. The approach is illustrated with a mixture of terpene molecules and a benchtop NMR spectrometer, paving the way to a sensitive, information-rich and affordable analytical method.     

Charge transfer complexes of picolines with sigma- and pi-acceptors

In the present study CT complexes of 2-, 3- and 4-Picolines with (DDQ) 2, 3-dichloro-5, 6-dicyano parabenzoquinone (pi-acceptor) and (I(2)) Iodine (sigma-acceptor) have been investigated spectrophotometrically in three different solvents (CCl(4), CHCl(3) and CH(2)Cl(2)) at six different temperatures. The formation constants of the CT complexes were determined by the Benesi-Hildebrand equation. The thermodynamic parameters were calculated by Van(')t Hoff equation. The DeltaH degrees , DeltaG degrees and DeltaS degrees values are all negative implying that the formation of studied complexes is exothermic in nature.     

Development of superconducting phases in BSCCO and Ba-BSCCO by sol spray process

The effects of barium substitution for Bi or Sr sites on the growth of superconducting phases have been studied. The sol spray process has been used to synthesis the Bi-Sr-Ca-Cu-O (BSCCO) and Ba-BSCCO homogeneous ceramic powders. Thermogravimetric (TG), differential thermal analysis (DTA), X-ray diffraction (XRD), scanning electron microscopy (SEM) techniques were employed to characterize the synthesized materials. The electrical resistance was measured by classical d.c. fourprobe technique. It has been observed that sol spray process has affected the physico-chemical properties of the materials and also avoid the use of chelating agent as in the case of sol gel process. In addition to the Bi₂Sr₂CaCu₂O₈ (2212) phase Ba doped specimens also contained Bi₂Sr₂Ca₂Cu₃O₁₀ (2223), BaBiO₃, BaCuO₂ and CuO phases. The results revealed that the specific effect of barium-doping on either sites (Bi or Sr) seems to avoid the formation of higher volume fraction of the low T _c phase and promoting the formation of BiBaO₃, BaCuO₂ and CuO along with formation of a high T _c 2223 phase. The substitution of Ba on either sites (Bi or Sr) lower the sintering temperature for the formation of high T _c (small volume fraction) however, the Ba doped specimens also contained non-superconducting phases.     

Exchange bias and magnetothermal properties in Fe@Mn nanocomposites

We have studied the Exchange Bias (EB) effect in nanocomposite films consisting of Fe nanoparticles (mean size ∼1.9 nm) embedded in an antiferromagnetic Mn matrix. They were produced by co-deposition through a gas aggregation cluster source and molecular beam epitaxy and have different Fe volume filling fractions (2.2% and 24.8%). The exchange field, higher in the sample with higher Fe concentration (at T=5 K, H_ex∼460 Oe for 24.8% and ∼310 Oe for 2.2% ), in both the samples decreases with increasing T, finally disappearing at T∼40 K. The EB properties have been studied in conjunction with results on the thermal dependence of the magnetic coercivity, zero-field-cooled and field-cooled magnetization and thermoremanence. The different Fe content strongly affects the magnetothermal properties, featuring superparamagnetic relaxation in the diluted sample and a reentrant ferromagnet-type transition in the concentrated one. Hence, the EB properties of the two samples have been discussed in consideration of such peculiarities of the magnetic behavior and highlighting the role of the Mn matrix.     

Synthesis, magnetic and dielectric properties of Er-Ni doped Sr-hexaferrite nanomaterials for applications in High density recording media and microwave devices

A sol-gel combustion method has been successfully employed for the synthesis of Sr-hexaferrite nanomaterials doped with Er³⁺ and Ni²⁺ at strontium and iron sites, respectively. The X-ray diffraction analysis confirmed the single magnetoplumbite phase and the crystallite size was found to be in the range of 14-16 nm, suitable for obtaining signal-to-noise ratio in the high density recording media. The magnetic properties such as saturation magnetization (M_s), remanence (M_r) and coercivity (H_c) were calculated from hysteresis loops. M_s, M_r and H_c are observed to increase with the Er-Ni content. The dielectric constant (ε´) and dielectric loss (tan δ) is found to decrease with the increase in frequency and is explained on the basis of Maxwell-Wagner and Koops theory. The decrease in dielectric constant and dielectric loss but increase in saturation magnetization and remanence with Er-Ni content suggests that the materials are suitable for applications in microwave devices and high density recording media .     

Synthesis and Evaluation of Anti-HIV Activity of Mono- and Di-Substituted Phosphonamidate Conjugates of Tenofovir

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several classes of derivatives were synthesized. The synthesized compounds were characterized by 1H NMR, IR, UV, and mass spectrometry. In addition, several of the synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single round infection assay using TZM-bl cells at 100 ng/mL. TFV (1) was used as a positive control and inhibited HIV infection by 35%. Among all the evaluated compounds, the disubstituted heptanolyl ester alanine phosphonamidate with naphthol oleate (69), pentanolyl ester alanine phosphonamidate with phenol oleate (62), and butanolyl ester alanine phosphonamidate with naphthol oleate (87) ester conjugates of TFV were more potent than parent drug TFV with 79.0%, 76.5%, 71.5% inhibition, respectively, at 100 ng/mL. Furthermore, two fatty acyl amide conjugates of tenofovir alafenamide (TAF) were synthesized and evaluated for comparative studies with TAF and TFV conjugates. Tetradecanoyl TAF conjugate 95 inhibited HIV infection by 99.6% at 100 ng/mL and showed comparable activity to TAF (97–99% inhibition) at 10–100 ng/mL but was more potent than TAF when compared at molar concentration.