Novel Sophoridine Derivatives Bearing Phosphoramide Mustard Moiety Exhibit Potent Antitumor Activities In Vitro and In Vivo

Abstract

Novel mustard functionalized sophoridine derivatives were synthesized and evaluated for their cytotoxicity against of a panel of various cancer cell lines. They were shown to be more sensitive to S180 and H22 tumor cells with IC50 values ranging from 1.01–3.65 μM, and distinctly were more cytotoxic to cancer cells than normal cell L929. In addition, compounds 7a, 7c, and 7e displayed moderate tumor suppression without apparent organ toxicity in vivo against mice bearing H22 liver tumors. Furthermore, they arrested tumor cells in the G1 phase and induced cellular apoptosis. Their potential binding modes with DNA-Top I complex have also been investigated.

Keywords

• mustard functionalized sophoridine derivatives
• antitumor activity
• apoptosis