Document Type
Article
Publication Date
3-1-2014
Publication Title
Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry
Volume
13
Issue
1
First Page
17
Last Page
28
Abstract
The medicinal activity of COX-2 inhibitors are sufficiently beneficial to urge the search for new drug designs. This study presents 16 analogs of lumiracoxib and 10 analogs to valdecoxib having properties suitable as COX-2 inhibitors. For lumiracoxib analogs the mean Log P, polar surface area, and formula weight are 3.00, 70.46 A2, and 276.60, respectively. For valdecoxib analogs the mean Log P, polar surface area, and formula weight are 3.65, 68.46 A2, and 322.32, respectively. Grubb’s test analysis of seven properties for seven known COX-2 selective inhibitors and those of 26 analog compounds indicated no outliers. The unpaired t-test compared Log P and polar surface area of seven known COX-2 inhibitors to all 26 analogs and found no difference. All 26 analogs showed no violation of the Rule of 5, this being an indicator of favorable bioavailability. Hierarchical cluster analysis by single linkage indicated lumiracoxib is most similar to analogs 2, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, and 17. Valdecoxib has highest similarity to analogs 8, 19, 21, 22, 23, 26, 27, and 28. Multiple regression analysis successfully produced equations for prediction of similar compounds to lumiracoxib and valdecoxib. Path analysis indicated that number of atoms, oxygen & nitrogen atoms, and Log P are the greatest determinants for formula weight for known COX-2 inhibitors. Criteria for molecular properties is established for identifying COX-2 inhibitors. These 26 analogs show much potential for active COX-2 inhibition.
Recommended Citation
Bartzatt, R. (2014). Drug analogs of COX-2 selective inhibitors Lumiracoxib and Valdescoib derived from in silico search and optimization. Anti-Inflammatory & Anti-Allergy in Medicinal Chemistry, 13(1), 17-28. DOI: 10.2174/18715230113129990019
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
The published manuscript is available at EurekaSelect in Anti-Inflammatory & Anti-Allergy in Medicinal Chemistry via http://www.eurekaselect.com/10.2174/18715230113129990019