| 1. |
- Musa, Klefah A. K., et al.
(författare)
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New nonsteroidal anti-inflammatory molecules with reduced photodegradation side effects and enhanced COX-2 selectivity
- 2011
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Ingår i: International Journal of Quantum Chemistry. - : Wiley-Blackwell. - 0020-7608 .- 1097-461X. ; 111:6, s. 1184-1195
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Tidskriftsartikel (refereegranskat)abstract
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as antipyretic, analgesic, and anti-inflammatory agents. However, they are also associated with a range of side effects, from phototoxicity due to excited state induced decarboxylation to severe conditions in the gastrointestinal tract caused by inhibition of the COX-1 isoform of the target cyclooxygenase enzyme. In the current work, new derivatives of the three NSAIDs ketoprofen, ibuprofen, and naproxen were designed. Their photochemistry was explored using hybrid-density functional theory (B3LYP/6-31G(d,p)) and time-dependent (TD) DFT, showing that the compounds will have significantly reduced propensity to decarboxylate from the first excited triplet state. In addition, docking studies were carried out for these new molecules to explore their activity and selectivity toward the two isoforms of the COX enzyme. The results show that most compounds have increased activity toward the COX enzymes, and in general are more selective toward the COX-2 target isoform. The results from this study suggest that the new modified molecules could be used in the future as NSAIDs with considerably reduced side effects.
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| 2. |
- Napolitano, C., et al.
(författare)
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Synthesis, kinase activity and molecular modeling of a resorcylic acid lactone incorporating an amide and a trans-enone in the macrocycle
- 2012
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 68:27-28, s. 5533-5540
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Tidskriftsartikel (refereegranskat)abstract
- Details for the synthesis of a resorcylic acid lactone (RAL) incorporating a trans-enone and an amide in the macrocyclic ring are provided herein. The sequence included the assembly of three fragments by esterification, olefination, and lactamization. The RAL with the lactam was less potent as an inhibitor of kinases than other RALs investigated. The biological results were rationalized by docking and molecular dynamics simulations of the lactam bound to human ERK2 and comparison with hypothemycin. (c) 2012 Elsevier Ltd. All rights reserved.
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| 3. |
- Ni, Gaofeng, et al.
(författare)
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Microbial Community and Metabolic Activity in Thiocyanate Degrading Low Temperature Microbial Fuel Cells
- 2018
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Thiocyanate is a toxic compound produced by the mining and metallurgy industries that needs to be remediated prior to its release into the environment. If the industry is situated at high altitudes or near the poles, economic factors require a low temperature treatment process. Microbial fuel cells are a developing technology that have the benefits of both removing such toxic compounds while recovering electrical energy. In this study, simultaneous thiocyanate degradation and electrical current generation was demonstrated and it was suggested that extracellular electron transfer to the anode occurred. Investigation of the microbial community by 16S rRNA metatranscriptome reads supported that the anode attached and planktonic anolyte consortia were dominated by a Thiobacillus-like population. Metatranscriptomic sequencing also suggested thiocyanate degradation primarily occurred via the 'cyanate' degradation pathway. The generated sulfide was metabolized via sulfite and ultimately to sulfate mediated by reverse dissimilatory sulfite reductase, APS reductase, and sulfate adenylyltransferase and the released electrons were potentially transferred to the anode via soluble electron shuttles. Finally, the ammonium from thiocyanate degradation was assimilated to glutamate as nitrogen source and carbon dioxide was fixed as carbon source. This study is one of the first to demonstrate a low temperature inorganic sulfur utilizing microbial fuel cell and the first to provide evidence for pathways of thiocyanate degradation coupled to electron transfer.
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