Design and synthesis of novel artemisinin derivatives with potent activities against colorectal cancer in vitro and in vivo.

A series of novel derivatives of artemisinin-4-(arylamino)quinazoline have been designed and synthesized, and most of them showing potent in vitro cytotoxic activity against HCT116 and WM-266-4 cell lines. Compound 32 was the most active derivative against HCT116 cell line with an IC₅₀ of 110 nM, and significantly improved the antitumor activity of the parent compounds dihydroartemisinin (DHA) (IC₅₀ = 2.85 μM) and Gefitinib (IC₅₀ = 19.82 μM). In vivo HCT116 xenografts assay showed that compound 32 exhibited potent antitumor activity with obvious tumor growth delay and tumor shrunken after 18 days treatment on xenografted mice, and especially without loss of body weight. Our results indicate that compounds 32 may represent a safe, novel structural lead for developing new chemotherapy of colorectal cancer.