98-97-5Relevant articles and documents
Specificity and mechanism of acinetobacter baumanii nicotinamidase: Implications for activation of the front-line tuberculosis drug pyrazinamide
Fyfe, Paul K.,Rao, Vincenzo A.,Zemla, Aleksandra,Cameron, Scott,Hunter, William N.
, p. 9176 - 9179 (2009)
TB or not TB active: The high-resolution crystal structures (see picture) of the zinccontaining metalloenzyme nicotinamidase in complex with nicotinic acid and pyrazinoic acid reveal new aspects of enzyme mechanism that help to explain the activation of a
Synthesis and spectroscopic study of three new oxadiazole derivatives with detailed computational evaluation of their reactivity and pharmaceutical potential
Mary, Y. Sheena,Miniyar, Pankaj B.,Mary, Y. Shyma,Resmi,Panicker, C. Yohannan,Armakovi?, Stevan,Armakovi?, Sanja J.,Thomas, Renjith,Sureshkumar
, p. 469 - 480 (2018)
Local reactivity properties and potential for application in new pharmaceutical compounds have been addressed for the three newly synthetized oxadiazole derivatives (2-(5-(2-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (ORTHONITRO), 2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (METANITRO) and 2-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (PARANITRO), by application of computational molecular modeling. Within the framework of density functional theory (DFT) this study encompassed calculations of molecular electrostatic potential (MEP), average local ionization energies (ALIE) and bond dissociation energies for hydrogen abstraction (H-BDE). MD simulations have been used in order to assess the influence of water and to identify the atoms of these molecules with preference towards the interaction with water molecules. Molecular docking procedure has been applied in order to check the binding activity of these derivatives against the Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor proteins. The pharmaceutical potential of these derivatives has been assessed by the calculations of the well-established drug likeness parameters. A strong out-of-plane CH mode of the phenyl rings are observed at 769 cm?1 for ORTHONITRO, 768 cm?1 for METANITRO and at 848 cm?1 for PARANITRO in the IR spectrum as expected for substituted benzenes. The VCD signals, corresponding to C[dbnd]N and NO2 modes of the title compounds are good markers for assigning of absolute configuration. In the title compounds, in ORTHONITRO, the oxadiazole ring is tilted from the phenyl and pyrazine ring while for METANITRO and PARANITRO, there is a planar orientation. The first hyperpolariazabilities of ORTHONITRO, METANITRO and PARANITRO are respectively, 34.83, 54.50 and 174.05 times that of urea. For all the compounds, HOMO is delocalized over the pyrazine and oxadiazole rings, while LUMO is delocalized over whole molecule, except pyrazine ring of ORTHONITRO, over phenyl ring and NO2 group of METANITRO and in the entire molecule of PARANITRO. The title compounds are docked with the proteins, Glucan endo-1.6-beta-glucosidase inhibitor, Acrocylindropepsin inhibitor and Chymosin inhibitor and METANITRO exhibits more inhibitory activity against the receptors than the other ligands. The results obtained from anti-TB activity are more promising as the compounds were found to be more potent than reference standard, ORTHONITRO (MIC = 1.6 μg/ml), METANITRO (MIC = 0.8 μg/ml), PARANITRO (MIC = 1.6 μg/ml), streptomycin (MIC = 6.2 μg/ml) and pyrazinamide (MIC = 3.1 μg/ml).
Hederagenin compound H-X with anti-lung cancer effect and preparation method and application thereof
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Paragraph 0048; 0049; 0051; 0052; 0120; 0121, (2020/04/17)
The invention provides a hederagenin compound H-X with an anti-tumor effect and a preparation method and application thereof. The structural general formula 1 is shown in the specifications. Most of the derivatives provided by the invention have obvious inhibition effects on tumor cells A549, MCF-7 and HepG2, and the compound hederagenin-2, 6-dimethylpyrazine (H-08) shows good selectivity betweentumors and normal conditions, especially on lung cancer A549 cells. The IC50 of the compound to A549, MCF-7, HepG2, MDCK and H9c2 is 3.45+/-0.59 muM, 8.73+/-1.49 muM, 8.71+/-0.38 muM, 14.11+/-0.04 muM, and 16.69+/-0.12 muM, the inhibition effect on A549 cells is similar to that of a positive drug cis-platinum (IC50 is 3.85+/-0.63 muM), but the toxicity on MDCK and H9c2 is obviously lower than thatof cis-platinum.
Carboxylic acid complex and synthesis method thereof
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Paragraph 0029; 0030; 0039; 0040; 0049; 0050, (2017/07/20)
The invention discloses a carboxylic acid complex, belonging to the technical field of chemical synthesis. The carboxylic acid complex is composed of 30-50ml of anhydrous ethanol, 0.2-0.5 mol/L 2-methyl pyrazine, 1.25-1.6 mol/L potassium hydroxide solution and 5.0*10-5.0*10 mol/L catalyst. The synthesis method of the carboxylic acid complex comprises the following steps: S1: adding the 5.0*10-5.0*10 mol/L catalyst to react; S2: after the reaction finishes, carrying out vacuum filtration while the solution is hot; and S3: filtering the precipitate generated in the step S2, washing, and recrystallizing with hot water to obtain the solid carboxylic acid complex. The operating method is simple, and the carboxylic acid complex has high yield. The added catalyst converts oxygen molecules into an effective oxidizer, and thus, substitutes the expensive and polluting chemical oxidizer, thereby lowering the production cost, reducing the generation of three wastes and conforming to the energy-saving demand of clean production at present.
