Medicinal Chemistry Research

, Volume 26, Issue 6, pp 1279–1290 | Cite as

Podophyllum derivatives containing fluorine atom in the 3-position of 2-aminopyridine improved the antitumor activity by inducing P53-dependent apoptosis

  • Huai WangEmail author
Original Research


In previous work, we presented experimental and theoretical evidence that podophyllum derivatives substituted by chlorine atom in the 3-posititon of 2-aminopyridine exhibited significantly elevated potency. In this study, a series of podophyllum derivatives substituted in the 3-position of 2-aminopyridine, including methyl and fluorine groups, were synthesized. Their chemical structures were confirmed by the spectral (1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, electrospray ionization mass spectrometry) and elemental analyses. These derivatives were tested for their respective cytotoxicities in HeLa, BGC-823, A549, Huh7, and MCF-7 cells by MTT assay and the pharmacological results showed that most of them displayed potent cytotoxicities against at least one of the tested cancer cell lines. Structure–activity relationship study suggested that the introduction of the fluorine atom into the 3-posititon of 2-aminopyridine had enhanced the cytotoxicity against numerous tumor cells compared to the chlorine atom, while the methyl group did not. Furthermore, other biological experiments were consistent with the beneficial effect of fluorine atom substituent in the 3-position of 2-aminopyridine, which then inhibited the microtubule polymerization and activity of topoisomerase II when 2-amino-3-fluoropyridine substituted in podophyllotoxin and 4′-O-demethylepipodophyllotoxin, and that they work by effecting the target proteins which induce P53-dependent apoptosis.


Podophyllum derivatives 2-Aminopyridine Fluorine atom P53-dependent apoptosis 



This work was supported by Science and Technology Youth Project of Education Department in Jiangxi province (NO. GJJ150109). I would like to acknowledge and thank the professors (Yajie Tang, Hubei University of Technology; Zhanpeng Yuan, Wuhan University) for their essential help. I also wish to thank the editor, the associate editor, and those anonymous reviewers for their helpful comments and suggestions, which have led to an improvement of this article.

Compliance with ethical standards

Conflict of interest

The author declares that they have no competing interests.

Supplementary material

44_2017_1841_MOESM1_ESM.tif (9.8 mb)
Supplementary Figure
44_2017_1841_MOESM2_ESM.doc (4.6 mb)
Supplementary Information


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.School of Public HealthNanchang UniversityNanchangPeople’s Republic of China

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