Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing β-(5′,6′,7′-trimethoxy-2′-indolyl)acryloyl group Original Research Article

A series of A-ring pyrrole derivatives of duocarmycin bearing β-(5′,6′,7′-trimethoxy-2′-indolyl)acryloyl group were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. New Seg-B analogues bearing β-(5′,6′,7′-trimethoxy-2′-indolyl)acryloyl group containing double bond as spacer had lower peripheral blood toxicity than the derivatives bearing 5′,6′,7′-trimethoxyindole-2′-carboxyl group in Seg-B of the natural type. Moreover, most of them exhibited potent antitumor activity against in vivo murine tumor models.