- Drug-bearing supramolecular filament hydrogels as anti-inflammatory agents
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We report here on the covalent conversion of the anti-inflammatory agent ketoprofen into self-assembling prodrugs that enable the effective purification of ketoprofen enantiomers, the improved selectivity and potency of ketoprofen, as well as the formatio
- Chen, Zhipeng,Xing, Lei,Fan, Qin,Cheetham, Andrew G.,Lin, Ran,Holt, Barbara,Chen, Liwen,Xiao, Yanyu,Cui, Honggang
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- Design and Synthesis of Novel Nonsteroidal Anti-Inflammatory Drugs and Carbonic Anhydrase Inhibitors Hybrids (NSAIDs-CAIs) for the Treatment of Rheumatoid Arthritis
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We report the synthesis of a series of hybrid compounds incorporating 6- and 7-substituted coumarins (carbonic anhydrase, CA inhibitors) derivatized with clinically used NSAIDs (indomethacin, sulindac, ketoprofen, ibuprofen, diclofenac, ketorolac, etc., cyclooxygenase inhibitors) as agents for the management of rheumatoid arthritis (RA). Most compounds were effective in inhibiting the RA overexpressed hCA IX and XII, with KI values in the low nanomolar-subnanomolar ranges. The antihyperalgesic activity of such compounds was assessed by means of the paw-pressure and incapacitance tests using an in vivo RA model. Among all tested compounds, the 7-coumarine hybrid with ibuprofen showed potent and persistent antihyperalgesic effect up to 60 min after administration.
- Bua, Silvia,Di Cesare Mannelli, Lorenzo,Vullo, Daniela,Ghelardini, Carla,Bartolucci, Gianluca,Scozzafava, Andrea,Supuran, Claudiu T.,Carta, Fabrizio
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- Predicted multiple selected reaction monitoring to screen activated drug-mediated modifications on human serum albumin
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Metabolic activation of drugs frequently generates electrophilic products that may undergo covalent binding to biological macromolecules, such as proteins and DNA. The resulting covalent adducts are of considerable concern in drug discovery and developmen
- Osaki, Fumio,Goto, Takaaki,Lee, Seon Hwa,Oe, Tomoyuki
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- Enantiodifferentiation of ketoprofen by Japanese firefly luciferase from Luciola lateralis
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Recently, we found that firefly luciferase exhibited (R)-enantioselective thioesterification activity toward 2-arylpropanoic acids. In the case of Japanese firefly luciferase from Luciola lateralis (LUC-H), the E-value for ketoprofen was approximately 20. In this study, we used a spectrophotometric method to measure the catalytic activity of LUC-H. Using this method allowed us to judge the reaction efficiency easily. Our results confirmed that LUC-H exhibits enantioselective thioesterification activity toward a series of 2-arylpropanoic acids. The highest activity was observed with ketoprofen. We also observed high enzymatic activity of LUC-H toward long-chain fatty acids. These results were reasonable because LUC-H is homologous with long-chain acyl-CoA synthetase. To obtain further information about the enantiodifferentiation mechanism of the LUC-H catalyzed thioesterification of ketoprofen, we determined the kinetic parameters of the reaction relative to each of its three substrates: ketoprofen, ATP, and coenzyme A (CoASH). We found that whereas the affinities of each compound are not affected by the chirality of ketoprofen, enantiodifferentiation is achieved by a chirality-dependent difference in the kcat parameter.
- Kato, Dai-Ichiro,Tatsumi, Tomohiro,Bansho, Asami,Teruya, Keisuke,Yoshida, Hiromitsu,Takeo, Masahiro,Negoro, Seiji
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experimental part
p. 140 - 146
(2012/01/19)
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