Synthesis and antiviral screening of 2-(propylthio)-7-substituted-thiazolo[5,4-d]pyrimidines as anti-bovine viral diarrhea virus agents

7-Chloro-2-(propylthio)thiazolo[5,4-d]pyrimidine 4 was prepared and used as a precursor for synthesizing new derivatives of thiazolo[5,4-d]pyrimidine through the nucleophilic displacement of the chlorine atom by different types of amino derivatives. Reaction of compound 4 with primary and secondary amines produced the corresponding substituted amino derivatives. Reaction of 4 with hydrazine hydrate then followed by condensation with aromatic aldehydes afforded hydrazone derivatives. Reaction of 4 with hydrazine hydrate then followed by reaction with isothiocyanates gave the disubstituted thiosemicarbazides. Finally, treatment of 4 with hydrazine derivatives afforded the novel disubstituted hydrazine derivatives. Preliminary antiviral screening on the bovine viral diarrhea virus (BVDV) was carried out, which was classified as a member of the same family of Hepatitis C virus. The results indicated that some of the tested compounds exhibited anti-BVDV activity which may be suitable for a new lead molecule to design more potent anti-BVDV agents.     

Benzimidazole tethered thioureas as a new entry to elastase inhibition and free radical scavenging: Synthesis,molecular docking,and enzyme inhibitory kinetics

The porcine pancreatic elastase inhibition and free-radical scavenging play a crucial role in age progression. All the series of 10 newly synthesized benzimidazole thioureas ( 4a-j ) were assessed for elastase inhibition and radical scavenging activity to identify the suitable anti-aging ingredient for cosmetics products. The compounds 4e , 4f , 4g , and 4h showed inhibition better than the standard, while compound 4f showed the most significant elastase inhibition with the IC₅₀ value of 1.318 ± 0.025 μM compared with oleanic acid IC₅₀ 13.451 ± 0.014 used ±1.989 and 41.563 ± 0.824, respectively, as standard. Molecular docking studies were performed and the compound 4f showed binding energy of 7.2 kcal/mol. Kinetics studies revealed inhibition of the pancreatic elastase in a competitive manner. The relative binding energy and structure activity relationship (SAR) identified compound 4f as an effective inhibitor of porcine pancreatic elastase. Compounds 4e and 4i showed remarkable free-radical scavenging activity with SC₅₀ values of 26.421.     

Synthesis and antimicrobial evaluation of new 2-pyridinone and 2-iminochromene derivatives containing morpholine moiety

As trail to overcome on the antimicrobial drug-resistance problems, new functionalized 2-pyridinone and 2-iminochromene derivatives bearing morpholine moiety were designed and synthesized. The 2-pyridinone derivatives were obtained through the cyclization of cyanoacetohydrazone of 4-morpholinylacetophenone with 1,3-dicarbonyl compounds, α,β-unsaturated nitriles or 2-(arylidene)malononitriles. The 2-iminochromene derivatives were synthesized through the ring closure of cyanoacetohydrazonewith salicylaldehyde derivatives. The antibacterial and antifungal activities for the synthesized 2-pyridinone and 2-iminochromene derivatives were investigated. Most of the tested compounds showed moderate activity against P. vulgaris. Compounds 4a,b and 5a,b showed moderate activity against G −ve bacteria. All iminochromene derivatives showed moderate activity against C. albicans. Compound 8c was the most active compound.     

Selective complexation of alkali metal ions and nanotubular cyclopeptides: a DFT study

A density functional theory based on interaction of alkali metal cations (Li⁺, Na⁺, K⁺, Rb⁺ and Cs⁺) with cyclic peptides constructed from 3 or 4 alanine molecule (CyAla3 and CyAla4), has been investigated using mixed basis set (C, H, O, Li⁺, Na⁺ and K⁺ using 6-31+G(d), and the heavier cations: Rb⁺ and Cs⁺ using LANL2DZ). The minimum energy structures, binding energies, and various thermodynamic parameters of free ligands and their metal cations complexes have been determined with B3LYP and CAM-B3LYP functionals. The order of interaction energies were found to be Li⁺ > K⁺ > Na⁺ > Rb⁺ > Cs⁺ and Li⁺ > Na⁺ > K⁺ ? Rb⁺ > Cs⁺, calculated at CAM-B3LYP level for the M/CyAla3 and M/CyAla4 complexes, respectively. Their selectivity trend shows that the highest cation selectivity for Li⁺ over other alkali metal ions has been achieved on the basis of thermodynamic analysis. The main types of driving force host–guest interactions are investigated, the electron-donating O offers lone pair electrons to the contacting LP* of alkali metal cations.     

Evaluation of the antioxidant and anti-inflammatory activities of solvent extracts of Tricholepis chaetolepis (Boiss) Rech. f. whole plant

Abstract

The whole plant, Tricholepis chaetolepis, powder was investigated using proximate and fluorescence analysis along with determining the extractive values. Total phenolics, flavonoids and total protein contents of n-hexane, chloroform and methanolic extracts of the whole plant were also determined. The anti-diabetic activity of all the three extracts of the plant was determined by in vitro alpha-amylase inhibition assay. The anti-oxidant potential was evaluated using Phosophomolybdenum and DPPH methods. The anti-inflammatory potential of all extracts were determined by carrageenan-induced rat paw oedema model. The evaluation of the plant extracts exhibited the anti-diabetic, anti-oxidant, and anti-inflammatory activities in dose dependent fashion. The research concludes that Tricholepis chaetolepis extracts contain phenol, flavonoids, and tannins that show observable anti-oxidant and anti-diabetic potential. It is also concluded that the methanol extract of the plant showed the maximum effect against inflammation induced by carrageenan in rat paw oedema as compared with n-hexane and chloroform extracts.     

Ferroptosis: A New Road towards Cancer Management

Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management.     

Conformation of simple aromatic molecules

The conformation of five aromatic molecules were calculated using the atom-atom potentials method. The deformations of valency angles were not considered, and the conformations of some molecules were determined solely by the minimum interaction energy between non-bounded pairs of atoms. In case of molecules having π-bonds, the geometry of the isolated molecule was determined by the balance between the π-electron and the non-bonded energies. A comparison is made between the structure of molecules in the crystal form and the structure of the free molecules determined by conformational analysis. For terphenyl molecule which has different structures in the different phases, a calculation of the structure of molecule in crystal from was done theoretically using lattice energy minimization. Good agreement was found between structures obtained theoretically and experimentally.