Kleemiss, Florian; Justies, Aileen; Duvinage, Daniel; Watermann, Patrick; Ehrke, Eric; Sugimoto, Kunihisa; Fugel, Malte; Malaspina, Lorraine A.; Dittmer, Anneke; Kleemiss, Torsten; Puylaert, Pim; King, Nelly R.; Staubitz, Anne; Tzschentke, Thomas M.; Dringen, Ralf; Grabowsky, Simon; Beckmann, Jens (2020). Sila-Ibuprofen. Journal of medicinal chemistry, 63(21), pp. 12614-12622. American Chemical Society 10.1021/acs.jmedchem.0c00813
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The synthesis, characterization, biological activity,and toxicology of sila-ibuprofen, a silicon derivative of the most common nonsteroidal anti-inflammatory drug, is reported. The key improvements compared with ibuprofen are a four times higher solubility in physiological media and a lower melting enthalpy,which are attributed to the carbon−silicon switch. The improved solubility is of interest for postsurgical intravenous administration.A potential for pain relief is rationalized via inhibition experiments of cyclooxygenases I and II (COX-I and COX-II) as well as via a set of newly developed methods that combine molecular dynamics,quantum chemistry, and quantum crystallography. The binding affinity of sila-ibuprofen to COX-I and COX-II is quantified in terms of London dispersion and electrostatic interactions in the active receptor site. This study not only shows the potential of sila-ibuprofen for medicinal application but also improves our understanding of the mechanism of action of the inhibition process.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Kleemiss, Florian, Malaspina, Lorraine, Grabowsky, Simon |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
0022-2623 |
Publisher: |
American Chemical Society |
Language: |
English |
Submitter: |
Simon Grabowsky |
Date Deposited: |
28 Jan 2021 17:10 |
Last Modified: |
05 Dec 2022 15:43 |
Publisher DOI: |
10.1021/acs.jmedchem.0c00813 |
PubMed ID: |
32931274 |
BORIS DOI: |
10.48350/150614 |
URI: |
https://boris.unibe.ch/id/eprint/150614 |
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