The application of tandem aza-wittig reaction to synthesize artemisinin-guanidine hybrids and their anti-tumor activity.

Three series of novel artemisinin-guanidine hybrids 4a-4f, 8a-8h and 9a-9h have been facilely synthesized via four-component reaction (aza-Wittig reaction) and evaluated for their anti-tumor activities against A549, HT-29 and MDA-MB-231 cell lines in vitro. All of the tested compounds showed enhanced anti-tumor activities with IC(50) values ranging from 0.02 µM to 12.0 µM as compared to DHA (dihydroartemisinin). Among them, artemisinin derived dimers, compounds 9b (IC(50) = 0.05 µM), 9d (IC(50) = 0.06 µM) and 9f (IC(50) = 0.02 µM) were found to be most active against HT29 cells.