Structure--activity relationships of side-chain modified didemnins.
The synthesis and antitumor activity of a novel didemnin B analogue containing a psi[CH2NH] amide bond surrogate between N-Me-D-Leu7 and Pro8 are reported. The analogue shows activity (GI50 = 4 nM) comparable to that of didemnin B (GI50 = 13 nM) in the NCI-60 tumor cell screen. This result, along with new data from previously reported synthetic didemnin analogues, is discussed within the context of the side-chain SAR for didemnins.
Ding
X
X
Department of Chemistry, University of Pennsylvania, Philadelphia 19104-6323, USA.
Vera
M D
MD
Liang
B
B
Zhao
Y
Y
Leonard
M S
MS
Joullié
M M
MM
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018716:Molecular Mimicry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins