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Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2363–2374 | Cite as

Synthesis and molecular docking study of novel alizarin derivatives containing phosphoryl amino acid moiety as potential antitumor agents

Original Research
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Abstract

Series of novel alizarin and phosphoryl amino acid scaffold (4a4d, 8a8d) were synthesized and evaluated for the suppression of cancer cell proliferation in vitro against MGC-803, HepG2, T24, NCI-H460, and SK-OV-3 cell lines by standard 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay compared with commercial anticancer drug doxorubicin. Interestingly, all newly synthesized compounds exhibited relatively high cytotoxicity compared with alizarin and low cytotoxicity against human normal liver cell line HL-7702 cells. Especially, compound 8d showed the best cytotoxicity against SK-OV-3 cells with IC50 7.09 µM, which was slightly worse than that of drug doxorubicin. The cell apoptosis-inducing activity of representative compound 8d in SK-OV-3 cells revealed that the anticancer activity of this compound depended on apoptosis of cancer cells via regulation of Bcl-2 family members, activation of caspase-9 and caspase-3. Cell cycle analysis confirmed that compound 8d mainly arrested SK-OV-3 cells in G2 stage. In addition, molecular docking studies were performed to position compound 8d into the telomerase (5CQG) active site to determine the probable binding model.

Keywords

Alizarin Phosphoryl amino acid Antitumor Apoptosis Molecular docking 

Notes

Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81260472, 21101035 and 21362002), Special Research Found for the Doctoral Program of Higher Education (NO. 20134504110002), the State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China (CMEMR2016-B06), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (No. 1107047002).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1938_MOESM1_ESM.docx (594 kb)
Supplementary Information

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Ri-zhen Huang
    • 1
  • Le Jin
    • 1
  • Gui-yang Yao
    • 1
  • Wei-long Dai
    • 2
  • Xiao-chao Huang
    • 1
  • Zhi-Xin Liao
    • 1
  • Heng-shan Wang
    • 2
  1. 1.Department of Pharmaceutical Engineering, School of Chemistry and Chemical EngineeringSoutheast UniversityNanjingPeople’s Republic of China
  2. 2.State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal ResourcesSchool of Chemistry & Pharmaceutical Sciences of Guangxi Normal UniversityGuilinPeople’s Republic of China

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