Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study

The COVID-19 outbreak continues to spread worldwide at a rapid rate. Currently, the absence of any effective antiviral treatment is the major concern for the global population. The reports of the occurrence of various point mutations within the important therapeutic target protein of SARS-CoV-2 has elevated the problem. The SARS-CoV-2 main protease (Mpro) is a major therapeutic target for new antiviral designs. In this study, the efficacy of PF-00835231 was investigated (a Mpro inhibitor under clinical trials) against the Mpro and their reported mutants. Various in silico approaches were used to investigate and compare the efficacy of PF-00835231 and five drugs previously documented to inhibit the Mpro. Our study shows that PF-00835231 is not only effective against the wild type but demonstrates a high affinity against the studied mutants as well.     

<Emphasis Type="Italic">Q</Emphasis>-Switched Yb-Doped Fiber Ring Laser with a Saturable Absorber Based on a Graphene Polyvinyl Alcohol Film

We propose, design, and demonstrate a Q-switched ytterbium-doped fiber laser (YDFL) employing a thin graphene polyvinyl alcohol (PVA) film as a passive saturable absorber (SA). The graphene is synthesized by electrochemical exfoliation of graphite at room temperature in 1% sodium dodecyl sulfate (SDS) aqueous solution. Graphene flakes obtained from the process are mixed with PVA solution as the host polymer to produce a thin film, which acts as a passive Q-switcher in the YDFL ring cavity. The laser generates a stable pulse operating at a wavelength of 1,076.4 nm with a threshold pump power of 73.7 mW. At a maximum 980 nm pump power of 113.6 mW, the YDFL generates an optical pulse train with a repetition rate of 25.53 kHz and a pulse width of 10 μs. The maximum pulse energy of 50.9 nJ is obtained at a pump power of 109.9 mW. A higher-performance Q-switched YDFL is expected to be achieved with optimization of the graphene saturable absorber and the laser cavity.     

Chromatographic identification of “green capping agents” extracted from Nasturtium officinale (Brassicaceae) leaves for the synthesis of MoO3 nanoparticles

A low‐temperature, efficient and effective method was investigated for phytochemical hydroethanolic extraction of Nasturtium officinale (Brassicaceae). The phytocompounds of the selected plant leaves were identified by high‐performance liquid chromatography, gas chromatography with mass spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet‐visible spectroscopy. Acetic acid, d ‐alanine, octodrine, decanoic acid, and cyclohexylethylamine were the major phytocompounds identified in N. officinale leaves with high similarity match and spectral purity. The reducing and stabilizing potential of the extracted phytochemicals was demonstrated by synthesizing the metal oxide nanoparticles (MoO₃) by treating ammonium heptamolybdate tetrahydrate (H₄MO₇N₆O₂₄.4H₂O) aqueous complex with bioactive compounds of the leaves. The bio‐synthesized MoO₃ nanoparticles were characterized by ultraviolet‐visible spectroscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, energy dispersive X‐ray spectroscopy, field emission‐scanning electron microscopy, and gas chromatography with mass spectroscopy. Gas chromatography‐mass spectroscopy identified acetic acid, d ‐alanine, and octodrine as stabilizing agents in the synthesis of MoO₃ nanoparticles.     

Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats

Alhagi camelorum (AC) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The overuse of cisplatin (Cis > 50 mg/m²) is associated with observed nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we investigated the nephroprotective effects of AC plant extract to prevent cisplatin-induced nephrotoxicity in albino Wistar rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and a significantly intense antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It is concluded that co-administration of cisplatin with AC extract showed exceptional nephroprotective effects at a dose of 600 mg/kg for Cis-induced nephrotoxicity.     

Dielectric Properties of Colossal-Dielectric-Constant Na1/2La1/2Cu3Ti4O12 Ceramics Prepared by Spark Plasma Sintering

In the current study, we report on the dielectric behavior of colossal-dielectric-constant Na_1/2La_1/2Cu₃Ti₄O₁₂ (NLCTO) ceramics prepared by mechanochemical synthesis and spark plasma sintering (SPS) at 850 °C, 900 °C, and 925 °C for 10 min. X-ray powder diffraction analysis showed that all the ceramics have a cubic phase. Scanning electron microscope observations revealed an increase in the average grain size from 175 to 300 nm with an increase in the sintering temperature. SPS NLCTO ceramics showed a room-temperature colossal dielectric constant (>10³) and a comparatively high dielectric loss (>0.1) over most of the studied frequency range (1 Hz–40 MHz). Two relaxation peaks were observed in the spectra of the electrical modulus and attributed to the response of grain and grain boundary. According to the Nyquist plots of complex impedance, the SPS NLCTO ceramics have semiconductor grains surrounded by electrically resistive grain boundaries. The colossal dielectric constant of SPS NLCTO ceramics was attributed to the internal barrier layer capacitance (IBLC) effect. The high dielectric loss is thought to be due to the low resistivity of the grain boundary of SPS NLCTO.     

Antioxidant,Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC₅₀ of 1.30 ± 0.05 mg/mL in the DPPH test and an EC₅₀ equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC₅₀) was 7.8 ± 0.3 μL EO/L, while the effective concentration in the ingestion test (LC₅₀) was 15.0 ± 2.1 μL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.     

An Update on Synthesis of Coumarin Sulfonamides as Enzyme Inhibitors and Anticancer Agents

Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique features of coumarin nucleus, in combination with privileged sulfonamide moiety, have enhanced the broad spectrum of biological activities. The research and development of coumarin, sulfonamide-based pharmacology, and medicinal chemistry have become active topics, and attracted the attention of medicinal chemists, pharmacists, and synthetic chemists. Coumarin sulfonamide compounds and analogs as clinical drugs have been used to cure various diseases with high therapeutic potency, which have shown their enormous development value. The diversified and wide array of biological activities such as anticancer, antibacterial, anti-fungal, antioxidant and anti-viral, etc. were displayed by diversified coumarin sulfonamides. The present systematic and comprehensive review in the current developments of synthesis and the medicinal chemistry of coumarin sulfonamide-based scaffolds give a whole range of therapeutics, especially in the field of oncology and carbonic anhydrase inhibitors. In the present review, various synthetic approaches, strategies, and methodologies involving effect of catalysts, the change of substrates, and the employment of various synthetic reaction conditions to obtain high yields is cited.     

Isolation and Identification of Bioactive Compounds from Bidens spp. Using HPLC-DAD and GC-MS Analysis and Their Biological Activity as Anticancer Molecules

The genus Bidens a member of family Compositae, is widely documented as an ethno-medicinally important genus of plants. In the present study, anticancer potential of three ethno-medicinally important species i.e., B. bipinnata, B. biternata and B. pilosa were tested. For in-vitro evaluation, an MTT (Thiazolyl blue tetrazolium bromide) assay was performed against cervical cancer cells (HeLa), hepatocellular carcinoma (HepG), and adenocarcinoma human alveolar basal epithelial cells (A549). For in vivo evaluation, Artemia salina, Danio rerio, and Caenorhabditis elegans were used. Among all the tested extracts, the ethanol extract of B. biternata appeared to have highest anticancer activity, and the compounds responsible for this activity were identified to be Tris (2,4-di-tert-butylphenyl), 4-hydroxy-2,4′-dimethoxychalcone, and 2,4-di-tert-butylphenol. This is the first report of the isolation of Tris (2,4-di-tert-butylphenyl) phosphate from the genus Bidens and the first report of 4-hydroxy-2,4′-dimethoxychalcone and 2,4-di-tert-butylphenol from B. biternata. Among the isolated compounds, 4-hydroxy-2,4′-dimethoxychalcone showed the highest anticancer activity with an LD50 value of 236.7 µg/mL. Therefore, this compound carries promising potential for being established as a pharmaceutical for chemoprevention and chemotherapy.