2. Academic Validation
  3. Synthesis and evaluation of a class of 1,4,7-triazacyclononane derivatives as iron depletion antitumor agents

Synthesis and evaluation of a class of 1,4,7-triazacyclononane derivatives as iron depletion antitumor agents

  • Bioorg Med Chem Lett. 2018 Jan 15;28(2):117-121. doi: 10.1016/j.bmcl.2017.11.048.
Sheng Wang 1,  Yongkang Gai 2,  Shasha Zhang 1,  Lei Ke 1,  Xiang Ma 3,  Guangya Xiang 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
  • 2 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 3 School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: xiangma@hust.edu.cn.
  • 4 School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: gyxiang1968@hotmail.com.
PMID: 29233652 DOI: 10.1016/j.bmcl.2017.11.048
Abstract

Iron depletion has been confirmed as an efficient strategy for Cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO2-PhPr-NE3TA and p-NH2-PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular Cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA. All these 1,4,7-triazacyclononane-based chelators exhibited much stronger antiproliferative activity than DFO and DTPA. Among them, chelators with phenylpropyl side chains, represented by p-NO2-PhPr-NE3TA and p-NH2-PhPr-NE3TA, displayed the highest antiproliferative activity against HepG2 cells. Hence, these compounds are attractive candidates for the advanced study as iron depletion agents for the potential anti-cancer therapy, and could be further in conjugation with a targeting moiety for the future development in targeted iron depletion therapy.

Keywords

1,4,7-Triazacyclononane derivatives; Antitumor agents; Iron deprivation.

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