Design and semisynthesis of novel fredericamycin A derivatives with an improved antitumor profile.
We report the design, semisynthesis, and biological activity of a series of fredericamycin (1) derivatives. Within this series compound 1e combines low nanomolar cytotoxic potency in vitro, increased tumor cell line selectivity, and in vivo activity in a human xenograft model.
Abel
Ulrich
U
Santhera Pharmaceuticals, Im Neuenheimer Feld 518-519, 69120 Heidelberg, Germany.
Simon
Werner
W
Eckard
Peter
P
Hansske
Friedrich G
FG
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007546:Isoquinolines; D013141:Spiro Compounds; C016660:fredericamycin A