Antitumor activity of endoperoxide-iron chelator conjugates-design, synthesis and biological evaluation.
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.
Jiagsu Key Laboratoy of Preventive and Translational Medicine for Geratric Diseases, Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Xing
X
Yan
Jiagsu Key Laboratoy of Preventive and Translational Medicine for Geratric Diseases, Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Yang
Y
Yu
Jiagsu Key Laboratoy of Preventive and Translational Medicine for Geratric Diseases, Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Peng
P
Ji
Jiagsu Key Laboratoy of Preventive and Translational Medicine for Geratric Diseases, Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Hui
H
He
Jiagsu Key Laboratoy of Preventive and Translational Medicine for Geratric Diseases, Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China. Electronic address: qiaochunhua@suda.edu.cn.
Chunhua
C
Qiao
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010545:Peroxides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007502:Iron Chelating Agents; D010545:Peroxides
Anti-cancer; Conjugates; Endoperoxide; Iron chelator