Nitrile synthesis
Dotaz
Zobrazit nápovědu
Bacterial amidases and nitrile hydratases can be used for the synthesis of various intermediates and products in the chemical and pharmaceutical industries and for the bioremediation of toxic pollutants. The aim of this study was to analyze the expression of the amidase and nitrile hydratase genes of Rhodococcus erythropolis and test the stereospecific nitrile hydratase and amidase activities on chiral cyanohydrins. The nucleotide sequences of the gene clusters containing the oxd (aldoxime dehydratase), ami (amidase), nha1, nha2 (subunits of the nitrile hydratase), nhr1, nhr2, nhr3 and nhr4 (putative regulatory proteins) genes of two R. erythropolis strains, A4 and CCM2595, were determined. All genes of both of the clusters are transcribed in the same direction. RT-PCR analysis, primer extension and promoter fusions with the gfp reporter gene showed that the ami, nha1 and nha2 genes of R. erythropolis A4 form an operon transcribed from the Pami promoter and an internal Pnha promoter. The activity of Pami was found to be weakly induced when the cells grew in the presence of acetonitrile, whereas the Pnha promoter was moderately induced by both the acetonitrile or acetamide used instead of the inorganic nitrogen source. However, R. erythropolis A4 cells showed no increase in amidase and nitrile hydratase activities in the presence of acetamide or acetonitrile in the medium. R. erythropolis A4 nitrile hydratase and amidase were found to be effective at hydrolysing cyanohydrins and 2-hydroxyamides, respectively.
- MeSH
- amidohydrolasy metabolismus MeSH
- dehydratasy metabolismus MeSH
- DNA bakterií chemie genetika MeSH
- genetická transkripce MeSH
- hydroxylaminy metabolismus MeSH
- multigenová rodina MeSH
- nitrily metabolismus MeSH
- regulace genové exprese u bakterií * MeSH
- Rhodococcus enzymologie genetika MeSH
- sekvenční analýza DNA MeSH
- stanovení celkové genové exprese MeSH
- substrátová specifita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R=3,4-Cl), 9 (R=2-Cl) and 11 (R=4-CF3) showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC=6.25 µg/mL). It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig's plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R=3-CF3), 3 (R=3,4-Cl) and 11 (R=4-CF3). A linear dependence between lipophilicity and herbicidal activity was observed.
- MeSH
- antituberkulotika chemická syntéza farmakologie MeSH
- chloroplasty účinky léků metabolismus MeSH
- fotosyntéza účinky léků MeSH
- halogenace MeSH
- herbicidy chemická syntéza farmakologie MeSH
- inhibiční koncentrace 50 MeSH
- mikrobiální testy citlivosti MeSH
- mikrovlny MeSH
- Mycobacterium smegmatis účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- nitrily chemická syntéza farmakologie MeSH
- pyraziny chemická syntéza farmakologie MeSH
- Spinacia oleracea účinky léků metabolismus MeSH
- transport elektronů účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- mepamil,
- MeSH
- nitrily farmakologie MeSH
- vápník antagonisté a inhibitory MeSH
- verapamil * analogy a deriváty farmakologie MeSH
- MeSH
- estrogeny biosyntéza MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- inhibitory aromatasy aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- nádory prsu farmakoterapie MeSH
- nitrily aplikace a dávkování terapeutické užití MeSH
- potkani Sprague-Dawley MeSH
- premenopauza účinky léků MeSH
- statistika jako téma metody MeSH
- triazoly aplikace a dávkování terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
The bengazoles are marine natural products with unique structure, containing two oxazole rings flanking a single carbon. They show very potent antifungal activity. The total syntheses of bengazole C and E are described following a convergent route which involves diastereoselective cycloaddition of an appropriately substituted nitrile oxide with a butane-1,2-diacetal-protected alkenediol as the key step.
Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are introduced from their nitrile precursors through late-stage functionalization. In this work, we propose a novel strategy involving the use of diversely protected, unprecedented tetrazole aldehydes as building blocks. This approach facilitates the incorporation of the tetrazole group into multicomponent reactions or other chemistries, aiding in the creation of a variety of complex, drug-like molecules. These innovative tetrazole building blocks are efficiently and directly synthesized using a Passerini three-component reaction (PT-3CR), employing cost-effective and readily available materials. We further showcase the versatility of these new tetrazole building blocks by integrating the tetrazole moiety into various multicomponent reactions (MCRs), which are already significantly employed in drug discovery. This technique represents a unique and complementary method to existing tetrazole synthesis processes. It aims to meet the growing demand for tetrazole-based compound libraries and novel scaffolds, which are challenging to synthesize through other methods.
- Publikační typ
- časopisecké články MeSH
Solasodine analogues containing a seven-membered F ring with a nitrogen atom placed at position 22a were prepared from diosgenin or tigogenin in a four-step synthesis comprising of the simultaneous opening of the F-ring and introduction of cyanide in position 22α, activation of the 26-hydroxyl group as mesylate, nitrile reduction, and N-cyclization. Solasodine, six obtained 22a(N)-homo analogues, as well as four 26a-homosolasodine derivatives and their open-chain precursors (13 in total) were tested as potential inhibitors of acetyl- and butyryl-cholinesterases and showed activity at micromolar concentrations. The structure-activity relationship study revealed that activities against studied esterases are affected by the structure of E/F rings and the substitution pattern of ring A. The most potent compound 8 acted as non-competitive inhibitors and exerted IC50 = 8.51 μM and 7.05 μM for eeAChE and eqBChE, respectively. Molecular docking studies revealed the hydrogen bond interaction of 8 with S293 of AChE; further rings are stabilized via hydrophobic interaction (ring A) or interaction with Y341 and W286 (rings B and C). Biological experiments showed no neurotoxicity of differentiated SH-SY5Y cells. More importantly, results from neuroprotective assay based on glutamate-induced cytotoxicity revealed that most derivatives had the ability to increase the viability of differentiated SH-SY5Y cells in comparison to galantamine and lipoic acid assayed as standards. The newly synthesized solasodine analogues are able to inhibit and to bind cholinesterases in noncompetitive mode of inhibition and exhibited neuroprotection potential of differentiated neuroblastoma cells after Glu-induced toxicity.
- MeSH
- alkaloidy Solanaceí chemická syntéza chemie farmakologie MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- cholinesterasy chemie účinky léků MeSH
- diosgenin chemie MeSH
- dusík chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- neuroprotektivní látky chemická syntéza chemie farmakologie MeSH
- neurotoxické syndromy farmakoterapie enzymologie patologie MeSH
- simulace molekulového dockingu MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Three asymmetrical AChE reactivators with cyano-moiety and propane linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by nerve agent tabun and insecticide paraoxon was tested in vitro and compared to pralidoxime, HI-6, obidoxime, K027, and K048. According to the results, three compounds seem to be promising against paraoxon-inhibited AChE. Better results were obtained for bisquaternary substances at least with one oxime group in position four. None of tested substances was able to satisfactorily reactivate tabun-inhibited AChE at concentration applicable for in vivo experiments.
