2. Academic Validation
  3. Novel N-substituted sophoridinol derivatives as anticancer agents

Novel N-substituted sophoridinol derivatives as anticancer agents

  • Eur J Med Chem. 2014 Jun 23:81:95-105. doi: 10.1016/j.ejmech.2014.04.069.
Chong-Wen Bi 1,  Cai-Xia Zhang 1,  Ying-Hong Li 1,  Sheng Tang 1,  Hong-Bin Deng 1,  Wu-Li Zhao 1,  Zhen Wang 1,  Rong-Guang Shao 2,  Dan-Qing Song 3
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
  • 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: shaor@yahoo.com.
  • 3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China. Electronic address: songdanqingsdq@hotmail.com.
PMID: 24826818 DOI: 10.1016/j.ejmech.2014.04.069
Abstract

Using sophoridine (1) as the lead compound, a series of new N-substituted sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. SAR analysis indicated that introduction of a chlorobenzyl on the 12-nitrogen atom of sophoridinol might significantly enhance the antiproliferative activity. Of the newly synthesized compounds, sophoridinol analogue 9k exhibited a potent effect against six human tumor cell lines (liver, colon, breast, lung, glioma and nasopharyngeal). The mode of action of 9k was to inhibit the DNA Topoisomerase I activity, followed by the G0/G1 phase arrest. It also showed a moderate oral bioavailability and good safety in vivo. Therefore, compound 9k has been selected as a novel-scaffold lead for further structural optimizations or as a chemical probe for exploring Anticancer pathways of this kinds of compounds.

Keywords

Antiproliferative; Sophoridinic acid; Sophoridinol; Structure–activity relationship; Topoisomerase I.

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