Abstract

FTY720 inhibits various cancers through PP2A activation. The structure of FTY720 is also used as a basic structure for the design of sphingosine kinase (SK) inhibitors. We have synthesized derivatives using an amide chain in FTY720 with a phenyl backbone, and then compounds were screened by an MTT cell viability assay. The PP2A activity of compound 7 was examined. The phosphorylation levels of AKT and ERK, downstream targets of PP2A, in the presence of compound 7, were determined. Compound 7 may exhibit anticancer effects through PP2A activation rather than the mechanism by inhibition of SK1 in cancer cells. In the docking study of compound 7 and PP2A, the amide chain of compound 7 showed an interaction with Asn61 that was different from FTY720, which is expected to affect the activity of the compound.

Details

Title
Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation
Author
Shrestha, Jitendra 1 ; Ki, Sung Hwan 2   VIAFID ORCID Logo  ; Shin, Sang Mi 2 ; Kim, Seon Woong 1 ; Joo-Youn, Lee 3 ; Hee-Sook Jun 4   VIAFID ORCID Logo  ; Lee, Taeho 5 ; Kim, Sanghee 6   VIAFID ORCID Logo  ; Baek, Dong Jae 1 ; Eun-Young, Park 1 

1  College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea 
2  College of Pharmacy, Chosun University, Gwangju, 61452, Korea 
3  College of Pharmacy, Seoul National University, Seoul 08826, Korea; Korea Chemical Bank, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea 
4  Lee Gil Ya Cancer and Diabetes Institute, Department of Molecular Medicine, Gachon University, Incheon 21999, Korea; College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Korea 
5  College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea 
6  College of Pharmacy, Seoul National University, Seoul 08826, Korea 
First page
2750
Publication year
2018
Publication date
2018
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.3390/molecules23112750
ProQuest document ID
2582849025
Copyright
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.