Synthesis and Biological Screening of Silicon-Containing Ibuprofen Derivatives: A Study of Their NF-κβ Inhibitory Activity, Cytotoxicity, and Their Ability to Bind IKKβ

David J. Pérez; Uzma I. Zakai; Song Guo; Ilia A. Guzei; Zeferino Gómez-Sandoval; Rodrigo Said Razo-Hernández; Robert West; Ángel Ramos-Organillo

doi:10.1071/CH15527

RESEARCH ARTICLE

Synthesis and Biological Screening of Silicon-Containing Ibuprofen Derivatives: A Study of Their NF-κβ Inhibitory Activity, Cytotoxicity, and Their Ability to Bind IKKβ

David J. Pérez ^A ^B , Uzma I. Zakai ^B ^E , Song Guo ^C , Ilia A. Guzei ^D , Zeferino Gómez-Sandoval ^A , Rodrigo Said Razo-Hernández ^A , Robert West ^B and Ángel Ramos-Organillo ^A ^E

+ Author Affiliations

- Author Affiliations

^A Facultad de Ciencias Químicas, Universidad de Colima, km 9 carretera Colima-Coquimatlán, Coquimatlán, Colima. CP 28400, México.

^B The Organosilicon Research Center, Department of Chemistry, 1101 University Avenue, Madison, WI 53706, USA.

^C Carbone Cancer Center, Wisconsin Institutes for Medical Research, 1111 Highland Avenue, Madison, WI 53705, USA.

^D Molecular Structure Laboratory Department of Chemistry, 1101 University Avenue, Madison, WI 53706, USA.

^E Corresponding authors. Email: zakaiu@yahoo.com; aaramos@ucol.mx

Australian Journal of Chemistry 69(6) 662-671 https://doi.org/10.1071/CH15527
Submitted: 27 August 2015 Accepted: 12 October 2015 Published: 13 November 2015

Abstract

The synthesis and characterisation of new silicon-containing amides and esters derived from ibuprofen is reported. These compounds were tested against nuclear transcription factor κβ (NF-κβ). Higher inhibition values than those of ibuprofen were achieved by the new amides 10a–10d; ester derivatives did not show inhibitory activity. The cytotoxicity of these new derivatives was screened; none of them displayed significant toxicity at the screened doses. A molecular docking calculation on IKKβ (an enzyme related to NF-κβ activation) was carried out and the results showed that the amides interact better than ibuprofen with key residues, which are important to the inhibition of IKKβ.

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Synthesis and Biological Screening of Silicon-Containing Ibuprofen Derivatives: A Study of Their NF-κβ Inhibitory Activity, Cytotoxicity, and Their Ability to Bind IKKβ

Abstract

References

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