Sila-Ibuprofen

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 and 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:

02 Feb 2021 16:20

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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