Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 6; p. 758
• Main Authors: Tian, Ye, Liang, Zhen, Xu, Hang, Mou, Yanhua, Guo, Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.06.2016; MDPI
• Subjects: anoxic; anticancer; Antigens, Neoplasm; artemisinin; Artemisinins - administration & dosage; Artemisinins - chemical synthesis; Artemisinins - chemistry; Cancer; carbonic anhydrase IX; Carbonic Anhydrase IX - antagonists & inhibitors; Cell Proliferation - drug effects; Click Chemistry; coumarin; Coumarins - administration & dosage; Coumarins - chemical synthesis; Coumarins - chemistry; Cytotoxicity; Design; Drug Design; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; HCT116 Cells; Humans; hybrid; Hybridization; Hydration; Magnetic Resonance Spectroscopy; Metastasis; Neoplasms - drug therapy; Pharmaceuticals; China; artemisinin; carbonic anhydrase IX; hybrid; coumarin; anoxic; anticancer; cytotoxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21060758

In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a-e, 11a-e, 12a-e, 13a-e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05-125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a-e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.