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Synthesis and Biological Evaluation of PF-543 Derivative

[ Vol. 16 , Issue. 1 ]

Author(s):

Seon Woong Kim, Taeho Lee, Joo-Youn Lee, Sanghee Kim, Hee-Sook Jun, Eun-Young Park* and Dong Jae Baek*   Pages 2 - 5 ( 4 )

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.

Affiliation:

College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, College of Pharmacy, Seoul National University, Seoul 08826, College of Pharmacy, Seoul National University, Seoul 08826, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554

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