Generic placeholder image

Letters in Organic Chemistry


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

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


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.

Graphical Abstract
Schnute, M.E.; McReynolds, M.D.; Kasten, T.; Yates, M.; Jerome, G.; Rains, J.W.; Hall, T.; Chrencik, J.; Kraus, M.; Cronin, C.N.; Saabye, M.; Highkin, M.K.; Broadus, R.; Ogawa, S.; Cukyne, K.; Zawadzke, L.E.; Peterkin, V.; Iyanar, K.; Scholten, J.A.; Wendling, J.; Fujiwara, H.; Nemirovskiy, O.; Wittwer, A.J.; Nagiec, M.M. Biochem. J., 2012, 444, 79-88.
Pyne, S.; Adams, D.R.; Pyne, N.J. Prog. Lipid Res., 2016, 62, 93-106.
French, K.J.; Zhuang, Y.; Maines, L.W.; Gao, P.; Wang, W.; Beljanski, V.; Upson, J.J.; Green, C.L.; Keller, S.N.; Smith, C.D. J. Pharmacol. Exp. Ther., 2010, 333, 129-139.
Pitman, M.R.; Costabile, M.; Pitson, S.M. Cell. Signal., 2016, 28, 1349-1363.
Lin, J.J.; Chang, T.; Cai, W.K.; Zhang, Z.; Yang, Y.X.; Sun, C.; Li, Z.Y.; Li, W.X. Neurochem. Int., 2015, 89, 92-100.
Rex, K.; Jeffries, S.; Brown, M.L.; Carlson, T.; Coxon, A.; Fajardo, F.; Frank, B.; Gustin, D.; Kamb, A.; Kassner, P.D.; Li, S.; Li, Y.; Morgenstern, K.; Plant, M.; Quon, K.; Ruefli-Brasse, A.; Schmidt, J.; Swearingen, E.; Walker, N.; Wang, Z.; Watson, J.E.; Wickramasinghe, D.; Wong, M.; Xu, G.; Wesche, H. PLoS One, 2013, 8, e68328.
Zhang, L.; Wang, H.D.; Ji, X.J.; Cong, Z.X.; Zhu, J.H.; Zhou, Y. Oncol. Rep., 2013, 30, 2571-2578.
White, C.; Alshaker, H.; Cooper, C.; Winkler, M.; Pchejetski, D. Oncotarget, 2016, 7, 23106-23127.
Lim, K.G.; Sun, C.; Bittman, R.; Pyne, N.J.; Pyne, S. Cell. Signal., 2011, 23, 1590-1595.
Baek, D.J.; MacRitchie, N.; Pyne, N.J.; Pyne, S.; Bittman, R. Chem. Commun. (Camb.), 2013, 49, 2136-2138.
Ju, T.; Gao, D.; Fang, Z.Y. Biochem. Biophys. Res. Commun., 2016, 470, 728-734.
Schnute, M.E.; McReynolds, M.D.; Carroll, J.; Chrencik, J.; Highkin, M.K.; Iyanar, K.; Jerome, G.; Rains, J.W.; Saabye, M.; Scholten, J.A.; Yates, M.; Nagiec, M.M. J. Med. Chem., 2017, 60, 2562-2572.
Schmieg, J.; Yang, G.; Franck, R.W.; Tsuji, M. J. Exp. Med., 2003, 198, 1631-1641.
Wang, J.; Knapp, S.; Pyne, N.J.; Pyne, S.; Elkins, J.M. ACS Med. Chem. Lett., 2014, 5, 1329-1333.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy