Antitumor activity of endoperoxide-iron chelator conjugates-design, synthesis and biological evaluation

作者：Yan Xing; Yu Yang; Ji Peng; He Hui; Qiao Chunhua^*

来源：European Journal of Medicinal Chemistry, 2015, 102: 180-187.

DOI：10.1016/j.ejmech.2015.07.040

• Anti-cancer
• Endoperoxide
• Iron chelator
• Conjugates

The effort to pursue effective anti-cancer drugs with novel mechanism of action has been continued for decades. As an antimalarial agent, artemisinin is well-known for its endoperoxide moiety, which is activated by the cellular iron. Meanwhile, the anti-cancer activity of artemisinin is recognized and reported. Herein, we report on the design, synthesis and evaluation of a series of endoperoxide and iron chelating moiety conjugates. Our study demonstrated that the endoperoxide-quinoline conjugates displayed effective antiproliferative capability and good selectivity against certain cancer cells, while both hydroxamate and catechol-endoperoxide conjugates shown no significant inhibitory activity. Preliminary mechanism investigation suggested that the antiproliferative activity of these conjugates is related to the endoperoxide moiety as well as their iron-chelating ability. These compounds are expected to be used as prototype for further development of selective anti-cancer drug candidate.

• 出版日期2015-9-18
• 单位苏州大学