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Synthesis and antitumor activity evaluation of anilinoquinoline derivatives by the effect on the expression of polo-like kinase

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third most common cause of cancer-related deaths. The objective of our research was to develop effective agents against HCC. Here, we have synthesized a series of anilinoquinoline derivatives. Based on a MTT assay and qRT-PCR in human Huh-7 hepatoma cells, we observed that 2-(2,6-dimethylanilino)quinoline (9) and 2-(3-benzenecarbonylanilino)quinoline (23) exhibited good antitumor activity. Besides, the polo-like kinase 1 (PLK1) positively correlated with aggressiveness of tumors and polo-like kinase 3 (PLK3) regarded as a tumor suppressor gene are serine/threonine kinases that play an essential role in carcinogenesis. Our results indicated that 2-anilinoquinoline (6) and 2-(3,5-dimethoxyanilino)quinoline (16) may decrease the expression levels of PLK1 gene, as well as increase the expression levels of PLK3 gene. We suggested this series of synthesized anilinoquinolines be promising to develop as novel regulating PLK molecular. Further, structural modification and the molecular mechanism of these compounds as a candidate are underway.

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Acknowledgments

Financial support of this work by the National Science Council of Taiwan is gratefully acknowledged. We also thank the National Center for High-Performance Computing for providing computer resources and chemical database services. This work was supported by the National Science Council of Taiwan (Grant Number: NSC96-2745-M-037-003-URD and NSC98-2119-M-037-001-MY3), Cancer Center, Kaohsiung Medical University Hospital, Taiwan (Grant Number: DOH100-TD-C-111-002), and Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Taiwan (Grant Number: KMU-EM-99-5-1).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Huang-Kai Peng, Li-Ya Wang & Shyh-Chyun Yang

  2. Department of Medical Laboratory Science and Biotechnology, College of Health Science, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    I-Ling Lin

  3. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan

    Chien-Chih Lee

  4. Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Cherng-Chyi Tzeng

  5. School of Medicine, China Medical University, Taichung, 404, Taiwan

    Jan-Gowth Chang

  6. Epigenome Research Center, China Medical University Hospital, Taichung, 404, Taiwan

    Jan-Gowth Chang

  7. Department of Laboratory Medicine, China Medical University Hospital, Taichung, 404, Taiwan

    Jan-Gowth Chang

  8. Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Shyh-Chyun Yang

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  1. Huang-Kai Peng
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  6. Jan-Gowth Chang
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Corresponding authors

Correspondence to Jan-Gowth Chang or Shyh-Chyun Yang.

Additional information

Huang-Kai Peng and I-Ling Lin contributed equally to this work.

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Peng, HK., Lin, IL., Lee, CC. et al. Synthesis and antitumor activity evaluation of anilinoquinoline derivatives by the effect on the expression of polo-like kinase. Med Chem Res 23, 1437–1446 (2014). https://doi.org/10.1007/s00044-013-0749-3

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  • DOI: https://doi.org/10.1007/s00044-013-0749-3

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