120th General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Exhibition Hall 2+3
Time 10월 19일 (목요일) 11:00~12:30
Code MEDI.P-296
Subject Theoretical investigation on oxidation potential analysis of tamoxifen derivatives
Authors Ji Young Park, Mu-Hyun Baik1,*
Institute for Basic Science, Korea
1Department of Chemistry, Korea Advanced Institute of Science and Technology, Korea
Abstract Tamoxifen, (Z)-2-[4-(1,2-diphenyl-1-butenyl)phenoxy-N,N-dimethylethanamine] , breast cancer drug, interrupts that estrogen molecule binds to estrogen receptor and inactivates estrogen receptor. Tamoxifen itself is the prodrug but it turns out to endoxifen after metabolism in liver. When Tamoxifen becomes endoxifen (N-desmethyl-4-hydroxytamoxifen), the binding activity with exstogen receptor increased as much as 30 – 100 times. Therefore the Oxidation activity of tamoxifen to endoxifen can be understood by oxidation potential between two species. From the various experiments, it is observed that metallocene tag decreases the oxidation potential of tamoxifen oxidation process. [1] Herein we theoretically investigated about the oxidation process of metallocene tag-attached tamoxifene derivatives, ferrocifen and cymantrene. By introducing ion-pairing model to this system, we could successfully describe experimental value and it has meaningful itself that how does ion-pair works with target molecule in the low dielectric media. After then we analyzed the electron density of oxidative species and figure out that which location is the most effective to control the oxidation potential of tamoxifene derivatives. From these studies, we could understand how does the metallocene tag decreases the oxidation potential and suggest potential candidates. Also we completed the reaction mechanism of tamoxifen under base condition, and conclude that which condition makes oxidation easier and drives to new-stable compound. [2] [1] K. Wu, S. Top, E. A. Hillard, G. Haouen, W. E. Geiger, Chem. Commun. 2011, 47, 10109-10111. [2] J. Y. Park, H. Nam, Y. Lee, W. E. Geiger, M.-H. Baik, manuscript in preparation (2017).
E-mail park.ji.young@ibs.re.kr