- Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor
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Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.
- Favia, Angelo D.,Habrant, Damien,Scarpelli, Rita,Migliore, Marco,Albani, Clara,Bertozzi, Sine Mandrup,Dionisi, Mauro,Tarozzo, Glauco,Piomelli, Daniele,Cavalli, Andrea,De Vivo, Marco
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p. 8807 - 8826,20
(2020/09/16)
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- Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof
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The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.
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- CORRELATION BETWEEN THE STRUCTURE AND ACTIVITY OF AMINOSTIGMINE DERIVATIVES CONTAINING VARIOUS SUBSTITUENTS AT THE NITROGEN ATOM OF THE CARBAMOYL GROUP
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Sixteen aminostigmine derivatives containing various substituents at the nitrogen atom of the carbamoyl group have been prepared, and their anticholine esterase activity in vitro, ionization constants, hydrophobicity, and toxicity have been determined.
- Prozorovskii, V. B.,Pavlova, L. V.,Suslova, I. M.,Belozerova, L. V.,Kokushkina, A. V.,Sazonova, A. V.
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p. 589 - 593
(2007/10/03)
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