1. Academic Validation
  2. Synthesis and biological evaluation of sophoridinol derivatives as a novel family of potential anticancer agents

Synthesis and biological evaluation of sophoridinol derivatives as a novel family of potential anticancer agents

  • ACS Med Chem Lett. 2014 Sep 22;5(11):1225-9. doi: 10.1021/ml500289h.
Chongwen Bi 1 Caixia Zhang 1 Yinghong Li 1 Sheng Tang 1 Shenggang Wang 2 Rongguang Shao 1 Haigen Fu 1 Feng Su 2 Danqing Song 1
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College , Beijing 100050, China.
  • 2 College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao 266042, China.
Abstract

New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 μM. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 μM·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant Cancer cells.

Keywords

Sophoridine; antiproliferative; drug resistance; sophoridinol; structure−activity relationship.

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