Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.     

Synthesis of Tacrine Analogs Derived from N-Aryl-5-amino-4-cyanopyrazoles

Synthesis of 11 tacrine analogs derived from N-aryl-5-amino-4-cyanopyrazoles, by a Friedländer type reaction, is described. Their structures were confirmed by ¹H and ¹³C NMR spectroscopy, elemental analysis, and/or mass spectrometry.     

Volatile oils from the plant and hairy root cultures of Ageratum conyzoides L

Two lines of hairy root culture of Ageratum conyzoides L. induced by Agrobacterium rhizogenes ATCC 15834 were established under either complete darkness or 16 h light/8 h dark photoperiod conditions. The volatile oil yields from aerial parts and roots of the parent plant, the hairy root culture photoperiod line and the hairy root culture dark line were 0.2%, 0.08%, 0.03% and 0.02%, (w/w), respectively. The compositions of the volatiles from the hairy roots, plant roots and aerial parts were analysed by GC and GC-MS. The main components of the volatiles from the hairy root cultures were β-farnesene, precocene I and β-caryophyllene, in different amounts, depending on light conditions and also on the age of cultures. Precocene I, β-farnesene, precocene II and β-caryophyllene were the main constituents of the volatile oils from the parent plant roots, whereas precocene I, germacrene D, β-caryophyllene and precocene II were the main constituents of the aerial parts of the parent plant. Growth and time-course studies of volatile constituents of the two hairy root lines were compared. Qualitative and quantitative differences were found between the volatile oils from the roots of the parent plant and those from the hairy roots.     

Synthesis,structural, magnetic and magnetocaloric properties of La0.8Sr0.2MnO3 nanoparticles

In this work, we reported a detailed study on the synthesis, structural and magnetic properties of nanocrystalline La_0.8Sr_0.2MnO₃. The synthesized nanoparticles were prepared using a sol–gel method and characterized using X-ray diffraction and high-resolution transmission electron microscope. The average particle size was found in the range from 40 to 45 nm. The magnetization versus temperature M(T) measurements as well as magnetization field dependence M(H) have been investigated using vibrating-sample magnetometer. The magnetization as a function of temperature M(T) indicated a broad second-order magnetic phase transition from ferromagnetic state to paramagnetic state in the Curie temperature region (320–340 K). The magnetocaloric effect of the sample has been estimated and presented a maximum magnetic entropy change |ΔS_M|_max?=?0.86 J kg^?1 K^?1 with relative cooling power?=?62.12 J kg^?1 at magnetic field (H)?=?2T. Based on the result of magnetocaloric properties, the investigated sample could be considered as a good refrigerant material for near room temperature magnetic refrigeration.

     

Synthesis of fluoromethylated materials derived from 2-trifluoromethyl acrylic acid phenethyl ester in an ionic liquid

Synthesis of fluoromethylated materials via Michael addition reaction catalyzed by l-proline in an ionic liquid, is described. Further, the synthesis and synthetic application of zinc reagents generated in an ionic liquid, giving trifluoromethylated materials, are described.     

Heterocyclic Synthesis with Nitriles: Synthesis of Pyrazolopyrimidine and Pyrazolopyridine Derivatives

The reaction of N ₁-substituted-5-amino-4-cyanopyrazoles with malononitrile and diethylmalonate occurs with formation of 6-substituted pyrazolo[3,4-d]pyrimidines, and pyrazolo[3,4-b]pyridines respectively. The structures of the products and conceivable mechanisms are discussed.     

N-Bromosuccinimide assisted oxidation of 5-aminopyrazoles: formation of bis diazenylderivatives

Treatment of 5-amino-4-cyanopyrazoles with N-bromosuccinimide, in DMF at rt gave azo dyes resulting from dimerization through the amino groups and further oxidation.With bromine water the dimer was also formed but, bromination occurred on the aryl ring, either at reflux or rt. Reduction of the azo group with zinc in acetic acid originated the corresponding pyrazoles.     

Studies with enaminonitriles: Synthesis and chemical reactivity of 2‐phenyl‐3‐piperidin‐1‐yl acrylonitrile under microwave heating

Benzyl cyanide reacts with triethylorthoformate and piperidine in DMF solution to yield the title compound 2 . This reacted with aromatic amines to yield either aminoacrylonitriles or quinoline depending on reaction conditions and substitution pattern on the aromatic amine. The reaction of compound 2 with hydrazine hydrate could only be effected in the microwave oven and resulted in the formation of aminopyrazole 7 . Diazotization of 7 and coupling with an active methylene reagent afforded pyrazolo[5,1‐c]‐[1,2,4]triazine derivatives.