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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Letter Article

Synthesis and Biological Evaluation of PF-543 Derivative

Author(s): Seon Woong Kim, Taeho Lee, Joo-Youn Lee, Sanghee Kim, Hee-Sook Jun, Eun-Young Park* and Dong Jae Baek*

Volume 16, Issue 1, 2019

Page: [2 - 5] Pages: 4

DOI: 10.2174/1570178615666181009121430

Price: $65

Abstract

PF-543 has been known as a substance that strongly inhibits SK1. However, it also exhibits antineoplastic activity that is lower than other inhibitors of SK1. In this study, we compared PF-543 and synthesized a newly designed derivative of PF-543 (compound 2) in which two aromatic structures were connected in para-form. The synthesized derivative showed inhibitory effect on SK1, similar to that of PF-543. However, it was more cytotoxic to HT29, AGS, and PC3 cells than PF-543. We also carried out a docking study for SK1 and demonstrated that the synthesized derivative showed interaction with SK1 similar to PF-543. Results obtained from this study suggest that the structure of compound 2 may be well substituted for the structure of PF-543 in terms of biological activity, providing us important structural information for the design of new derivatives of PF-543.

Keywords: PF-543, sphingosine kinase, inhibitor, anticancer, derivative, medicinal chemistry.

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